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Sample records for dysfunction bacterial proliferation

  1. Electrospun polystyrene fiber diameter influencing bacterial attachment, proliferation, and growth.

    PubMed

    Abrigo, Martina; Kingshott, Peter; McArthur, Sally L

    2015-04-15

    Electrospun materials have been widely investigated in the past few decades as candidates for tissue engineering applications. However, there is little available data on the mechanisms of interaction of bacteria with electrospun wound dressings of different morphology and surface chemistry. This knowledge could allow the development of effective devices against bacterial infections in chronic wounds. In this paper, the interactions of three bacterial species (Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus) with electrospun polystyrene meshes were investigated. Bacterial response to meshes with different fiber diameters was assessed through a combination of scanning electron microscopy (SEM) and confocal microscopy. Experiments included attachment studies in liquid medium but also directly onto agar plates; the latter was aimed at mimicking a chronic wound environment. Fiber diameter was shown to affect the ability of bacteria to proliferate within the fibrous networks, depending on cell size and shape. The highest proliferation rates occurred when fiber diameter was close to the bacterial size. Nanofibers were found to induce conformational changes of rod shaped bacteria, limiting the colonization process and inducing cell death. The data suggest that simply tuning the morphological properties of electrospun fibers may be one strategy used to control biofilm formation within wound dressings.

  2. Wakayama Symposium: Peroxisome Proliferator-Activated Receptor-gamma (PPARγ) and Meibomian Gland Dysfunction

    PubMed Central

    Jester, James V.; Brown, Donald J.

    2012-01-01

    Recently we have shown that mouse and human meibomian glands undergo specific age-related changes, including decreased acinar cell proliferation, acinar atrophy, and altered peroxisome proliferator-activated receptor gamma (PPARγ) localization from cytoplasmic-vesicular/nuclear in young mice and humans to nuclear in old mice and humans. Since PPARγ is a lipid-sensitive, nuclear receptor implicated in regulating adipocyte and sebocyte differentiation and lipogenesis, our findings suggest that PPARγ may be involved in modulating meibomian gland differentiation during aging. Based on these findings, we propose that aging of the meibomian gland results in downregulation of PPARγ, leading to decreased meibocyte differentiation and lipid synthesis, gland atrophy, and a hyposecretory meibomian gland dysfunction. PMID:23084144

  3. Inhibition of c-Jun-N-terminal Kinase Increases Cardiac Peroxisome Proliferator-activated Receptor α Expression and Fatty Acid Oxidation and Prevents Lipopolysaccharide-induced Heart Dysfunction*

    PubMed Central

    Drosatos, Konstantinos; Drosatos-Tampakaki, Zoi; Khan, Raffay; Homma, Shunichi; Schulze, P. Christian; Zannis, Vassilis I.; Goldberg, Ira J.

    2011-01-01

    Septic shock results from bacterial infection and is associated with multi-organ failure, high mortality, and cardiac dysfunction. Sepsis causes both myocardial inflammation and energy depletion. We hypothesized that reduced cardiac energy production is a primary cause of ventricular dysfunction in sepsis. The JNK pathway is activated in sepsis and has also been implicated in impaired fatty acid oxidation in several tissues. Therefore, we tested whether JNK activation inhibits cardiac fatty acid oxidation and whether blocking JNK would restore fatty acid oxidation during LPS treatment. LPS treatment of C57BL/6 mice and adenovirus-mediated activation of the JNK pathway in cardiomyocytes inhibited peroxisome proliferator-activated receptor α expression and fatty acid oxidation. Surprisingly, none of the adaptive responses that have been described in other types of heart failure, such as increased glucose utilization, reduced αMHC:βMHC ratio or induction of certain microRNAs, occurred in LPS-treated mice. Treatment of C57BL/6 mice with a general JNK inhibitor (SP600125) increased fatty acid oxidation in mice and a cardiomyocyte-derived cell line. JNK inhibition also prevented LPS-mediated reduction in fatty acid oxidation and cardiac dysfunction. Inflammation was not alleviated in LPS-treated mice that received the JNK inhibitor. We conclude that activation of JNK signaling reduces fatty acid oxidation and prevents the peroxisome proliferator-activated receptor α down-regulation that occurs with LPS. PMID:21873422

  4. Diabetic HDL is dysfunctional in stimulating endothelial cell migration and proliferation due to down regulation of SR-BI expression.

    PubMed

    Pan, Bing; Ma, Yijing; Ren, Hui; He, Yubin; Wang, Yongyu; Lv, Xiaofeng; Liu, Donghui; Ji, Liang; Yu, Baoqi; Wang, Yuhui; Chen, Y Eugene; Pennathur, Subramaniam; Smith, Jonathan D; Liu, George; Zheng, Lemin

    2012-01-01

    Diabetic HDL had diminished capacity to stimulate endothelial cell (EC) proliferation, migration, and adhesion to extracellular matrix. The mechanism of such dysfunction is poorly understood and we therefore sought to determine the mechanistic features of diabetic HDL dysfunction. We found that the dysfunction of diabetic HDL on human umbilical vein endothelial cells (HUVECs) was associated with the down regulation of the HDL receptor protein, SR-BI. Akt-phosphorylation in HUVECs was induced in a biphasic manner by normal HDL. While diabetic HDL induced Akt phosphorylation normally after 20 minutes, the phosphorylation observed 24 hours after diabetic HDL treatment was reduced. To determine the role of SR-BI down regulation on diminished EC responses of diabetic HDL, Mouse aortic endothelial cells (MAECs) were isolated from wild type and SR-BI (-/-) mice, and treated with normal and diabetic HDL. The proliferative and migratory effects of normal HDL on wild type MAECs were greatly diminished in SR-BI (-/-) cells. In contrast, response to diabetic HDL was impaired in both types suggesting diminished effectiveness of diabetic HDL on EC proliferation and migration might be due to the down regulation of SR-BI. Additionally, SR-BI down regulation diminishes diabetic HDL's capacity to activate Akt chronically. Diabetic HDL was dysfunctional in promoting EC proliferation, migration, and adhesion to matrix which was associated with the down-regulation of SR-BI. Additionally, SR-BI down regulation diminishes diabetic HDL's capacity to activate Akt chronically.

  5. Loss of COX5B inhibits proliferation and promotes senescence via mitochondrial dysfunction in breast cancer

    PubMed Central

    Jiang, Hong-Lin; Li, Liang-Dong; Hu, Xin; Xu, Xiao-En; Jin, Wei

    2015-01-01

    COX5B, a peripheral subunit of the cytochrome c oxidase complex, has previously been reported to maintain the stability of this complex. However, its functions and mechanisms involved in breast cancer progression remain unclear. Here, by performing SILAC assays in breast cancer cell models and detecting COX5B expression in tissues, we found that COX5B expression was elevated in breast cancer. Down-regulation of COX5B in breast cancer cell lines can suppress cell proliferation and induced cell senescence which was accompanied by elevating production of IL-8 and other cytokines. Interestingly, conditioned medium from COX5B knockdown cells could promote breast cancer cell migration. Mechanistic studies reveal that COX5B silence induces an increase in production of ROS, depolarization of MMP and a decrease in ATP. What's more, silence of COX5B leads to metabolic disorders, such as increased glucose uptake and decreased lactate secretion. Collectively, our study shows that loss of COX5B induces mitochondrial dysfunction and subsequently leads to cell growth suppression and cell senescence. Cytokines such as IL-8 secreted by senescent cells may in turn alter the microenvironment which could enhance cell migration. These findings may provide a novel paradigm for the treatment which combined anti-cancer drugs with particular cytokine inhibitors such as IL-8 blockers. PMID:26506233

  6. Loss of COX5B inhibits proliferation and promotes senescence via mitochondrial dysfunction in breast cancer.

    PubMed

    Gao, Shui-Ping; Sun, He-Fen; Jiang, Hong-Lin; Li, Liang-Dong; Hu, Xin; Xu, Xiao-En; Jin, Wei

    2015-12-22

    COX5B, a peripheral subunit of the cytochrome c oxidase complex, has previously been reported to maintain the stability of this complex. However, its functions and mechanisms involved in breast cancer progression remain unclear. Here, by performing SILAC assays in breast cancer cell models and detecting COX5B expression in tissues, we found that COX5B expression was elevated in breast cancer. Down-regulation of COX5B in breast cancer cell lines can suppress cell proliferation and induced cell senescence which was accompanied by elevating production of IL-8 and other cytokines. Interestingly, conditioned medium from COX5B knockdown cells could promote breast cancer cell migration. Mechanistic studies reveal that COX5B silence induces an increase in production of ROS, depolarization of MMP and a decrease in ATP. What's more, silence of COX5B leads to metabolic disorders, such as increased glucose uptake and decreased lactate secretion. Collectively, our study shows that loss of COX5B induces mitochondrial dysfunction and subsequently leads to cell growth suppression and cell senescence. Cytokines such as IL-8 secreted by senescent cells may in turn alter the microenvironment which could enhance cell migration. These findings may provide a novel paradigm for the treatment which combined anti-cancer drugs with particular cytokine inhibitors such as IL-8 blockers.

  7. SGLT1 activity in lung alveolar cells of diabetic rats modulates airway surface liquid glucose concentration and bacterial proliferation

    PubMed Central

    Oliveira, Tales Lyra; Candeia-Medeiros, Návylla; Cavalcante-Araújo, Polliane M.; Melo, Igor Santana; Fávaro-Pípi, Elaine; Fátima, Luciana Alves; Rocha, Antônio Augusto; Goulart, Luiz Ricardo; Machado, Ubiratan Fabres; Campos, Ruy R.; Sabino-Silva, Robinson

    2016-01-01

    High glucose concentration in the airway surface liquid (ASL) is an important feature of diabetes that predisposes to respiratory infections. We investigated the role of alveolar epithelial SGLT1 activity on ASL glucose concentration and bacterial proliferation. Non-diabetic and diabetic rats were intranasally treated with saline, isoproterenol (to increase SGLT1 activity) or phlorizin (to decrease SGLT1 activity); 2 hours later, glucose concentration and bacterial proliferation (methicillin-resistant Sthaphylococcus aureus, MRSA and Pseudomonas aeruginosa, P. aeruginosa) were analyzed in bronchoalveolar lavage (BAL); and alveolar SGLT1 was analyzed by immunohistochemistry. BAL glucose concentration and bacterial proliferation increased in diabetic animals: isoproterenol stimulated SGLT1 migration to luminal membrane, and reduced (50%) the BAL glucose concentration; whereas phlorizin increased the BAL glucose concentration (100%). These regulations were accompanied by parallel changes of in vitro MRSA and P. aeruginosa proliferation in BAL (r = 0.9651 and r = 0.9613, respectively, Pearson correlation). The same regulations were observed in in vivo P. aeruginosa proliferation. In summary, the results indicate a relationship among SGLT1 activity, ASL glucose concentration and pulmonary bacterial proliferation. Besides, the study highlights that, in situations of pulmonary infection risk, such as in diabetic subjects, increased SGLT1 activity may prevent bacterial proliferation whereas decreased SGLT1 activity can exacerbate it. PMID:26902517

  8. Vibrio vulnificus Secretes an Insulin-degrading Enzyme That Promotes Bacterial Proliferation in Vivo*

    PubMed Central

    Kim, In Hwang; Kim, Ik-Jung; Wen, Yancheng; Park, Na-Young; Park, Jinyoung; Lee, Keun-Woo; Koh, Ara; Lee, Ji-Hyun; Koo, Seung-Hoi; Kim, Kun-Soo

    2015-01-01

    We describe a novel insulin-degrading enzyme, SidC, that contributes to the proliferation of the human bacterial pathogen Vibrio vulnificus in a mouse model. SidC is phylogenetically distinct from other known insulin-degrading enzymes and is expressed and secreted specifically during host infection. Purified SidC causes a significant decrease in serum insulin levels and an increase in blood glucose levels in mice. A comparison of mice infected with wild type V. vulnificus or an isogenic sidC-deletion strain showed that wild type bacteria proliferated to higher levels. Additionally, hyperglycemia leads to increased proliferation of V. vulnificus in diabetic mice. Consistent with these observations, the sid operon was up-regulated in response to low glucose levels through binding of the cAMP-receptor protein (CRP) complex to a region upstream of the operon. We conclude that glucose levels are important for the survival of V. vulnificus in the host, and that this pathogen uses SidC to actively manipulate host endocrine signals, making the host environment more favorable for bacterial survival and growth. PMID:26041774

  9. Diabetic HDL Is Dysfunctional in Stimulating Endothelial Cell Migration and Proliferation Due to Down Regulation of SR-BI Expression

    PubMed Central

    Pan, Bing; Ma, Yijing; Ren, Hui; He, Yubin; Wang, Yongyu; Lv, Xiaofeng; Liu, Donghui; Ji, Liang; Yu, Baoqi; Wang, Yuhui; Chen, Y. Eugene; Pennathur, Subramaniam; Smith, Jonathan D.; Liu, George; Zheng, Lemin

    2012-01-01

    Background Diabetic HDL had diminished capacity to stimulate endothelial cell (EC) proliferation, migration, and adhesion to extracellular matrix. The mechanism of such dysfunction is poorly understood and we therefore sought to determine the mechanistic features of diabetic HDL dysfunction. Methodology/Principal Findings We found that the dysfunction of diabetic HDL on human umbilical vein endothelial cells (HUVECs) was associated with the down regulation of the HDL receptor protein, SR-BI. Akt-phosphorylation in HUVECs was induced in a biphasic manner by normal HDL. While diabetic HDL induced Akt phosphorylation normally after 20 minutes, the phosphorylation observed 24 hours after diabetic HDL treatment was reduced. To determine the role of SR-BI down regulation on diminished EC responses of diabetic HDL, Mouse aortic endothelial cells (MAECs) were isolated from wild type and SR-BI (−/−) mice, and treated with normal and diabetic HDL. The proliferative and migratory effects of normal HDL on wild type MAECs were greatly diminished in SR-BI (−/−) cells. In contrast, response to diabetic HDL was impaired in both types suggesting diminished effectiveness of diabetic HDL on EC proliferation and migration might be due to the down regulation of SR-BI. Additionally, SR-BI down regulation diminishes diabetic HDL’s capacity to activate Akt chronically. Conclusions/Significance Diabetic HDL was dysfunctional in promoting EC proliferation, migration, and adhesion to matrix which was associated with the down-regulation of SR-BI. Additionally, SR-BI down regulation diminishes diabetic HDL’s capacity to activate Akt chronically. PMID:23133640

  10. Increased expression of BDNF and proliferation of dentate granule cells after bacterial meningitis.

    PubMed

    Tauber, Simone C; Stadelmann, Christine; Spreer, Annette; Brück, Wolfgang; Nau, Roland; Gerber, Joachim

    2005-09-01

    Proliferation and differentiation of neural progenitor cells is increased after bacterial meningitis. To identify endogenous factors involved in neurogenesis, expression of brain-derived neurotrophic factor (BDNF), TrkB, nerve growth factor (NGF), and glial cell line-derived neurotrophic factor (GDNF) was investigated. C57BL/6 mice were infected by intracerebral injection of Streptococcus pneumoniae. Mice were killed 30 hours later or treated with ceftriaxone and killed 4 days after infection. Hippocampal BDNF mRNA levels were increased 2.4-fold 4 days after infection (p = 0.026). Similarly, BDNF protein levels in the hippocampal formation were higher in infected mice than in control animals (p = 0.0003). This was accompanied by an elevated proliferation of dentate granule cells (p = 0.0002). BDNF protein was located predominantly in the hippocampal CA3/4 area and the hilus of the dentate gyrus. The density of dentate granule cells expressing the BDNF receptor TrkB as well as mRNA levels of TrkB in the hippocampal formation were increased 4 days after infection (p = 0.027 and 0.0048, respectively). Conversely, NGF mRNA levels at 30 hours after infection were reduced by approximately 50% (p = 0.004). No significant changes in GDNF expression were observed. In conclusion, increased synthesis of BDNF and TrkB suggests a contribution of this neurotrophic factor to neurogenesis after bacterial meningitis.

  11. Reduced proliferation of endothelial colony-forming cells in unprovoked venous thromboembolic disease as a consequence of endothelial dysfunction

    PubMed Central

    Hernandez-Lopez, Rubicel; Chavez-Gonzalez, Antonieta; Torres-Barrera, Patricia; Moreno-Lorenzana, Dafne; Lopez-DiazGuerrero, Norma; Santiago-German, David; Isordia-Salas, Irma; Smadja, David; C. Yoder, Mervin; Majluf-Cruz, Abraham

    2017-01-01

    Background Venous thromboembolic disease (VTD) is a public health problem. We recently reported that endothelial colony-forming cells (ECFCs) derived from endothelial cells (EC) (ECFC-ECs) from patients with VTD have a dysfunctional state. For this study, we proposed that a dysfunctional status of these cells generates a reduction of its proliferative ability, which is also associated with senescence and reactive oxygen species (ROS). Methods and results Human mononuclear cells (MNCs) were obtained from peripheral blood from 40 healthy human volunteers (controls) and 50 patients with VTD matched by age (20−50 years) and sex to obtain ECFCs. We assayed their proliferative ability with plasma of patients and controls and supernatants of cultures from ECFC-ECs, senescence-associated β-galactosidase (SA-β-gal), ROS, and expression of ephrin-B2/Eph-B4 receptor. Compared with cells from controls, cells from VTD patients showed an 8-fold increase of ECFCs that emerged 1 week earlier, reduced proliferation at long term (39%) and, in passages 4 and 10, a highly senescent rate (30±1.05% vs. 91.3±15.07%, respectively) with an increase of ROS and impaired expression of ephrin-B2/Eph-4 genes. Proliferation potential of cells from VTD patients was reduced in endothelial medium [1.4±0.22 doubling population (DP)], control plasma (1.18±0.31 DP), or plasma from VTD patients (1.65±0.27 DP). Conclusions As compared with controls, ECFC-ECs from individuals with VTD have higher oxidative stress, proliferation stress, cellular senescence, and low proliferative potential. These findings suggest that patients with a history of VTD are ECFC-ECs dysfunctional that could be associated to permanent risk for new thrombotic events. PMID:28910333

  12. Reduced proliferation of endothelial colony-forming cells in unprovoked venous thromboembolic disease as a consequence of endothelial dysfunction.

    PubMed

    Hernandez-Lopez, Rubicel; Chavez-Gonzalez, Antonieta; Torres-Barrera, Patricia; Moreno-Lorenzana, Dafne; Lopez-DiazGuerrero, Norma; Santiago-German, David; Isordia-Salas, Irma; Smadja, David; C Yoder, Mervin; Majluf-Cruz, Abraham; Alvarado-Moreno, J Antonio

    2017-01-01

    Venous thromboembolic disease (VTD) is a public health problem. We recently reported that endothelial colony-forming cells (ECFCs) derived from endothelial cells (EC) (ECFC-ECs) from patients with VTD have a dysfunctional state. For this study, we proposed that a dysfunctional status of these cells generates a reduction of its proliferative ability, which is also associated with senescence and reactive oxygen species (ROS). Human mononuclear cells (MNCs) were obtained from peripheral blood from 40 healthy human volunteers (controls) and 50 patients with VTD matched by age (20-50 years) and sex to obtain ECFCs. We assayed their proliferative ability with plasma of patients and controls and supernatants of cultures from ECFC-ECs, senescence-associated β-galactosidase (SA-β-gal), ROS, and expression of ephrin-B2/Eph-B4 receptor. Compared with cells from controls, cells from VTD patients showed an 8-fold increase of ECFCs that emerged 1 week earlier, reduced proliferation at long term (39%) and, in passages 4 and 10, a highly senescent rate (30±1.05% vs. 91.3±15.07%, respectively) with an increase of ROS and impaired expression of ephrin-B2/Eph-4 genes. Proliferation potential of cells from VTD patients was reduced in endothelial medium [1.4±0.22 doubling population (DP)], control plasma (1.18±0.31 DP), or plasma from VTD patients (1.65±0.27 DP). As compared with controls, ECFC-ECs from individuals with VTD have higher oxidative stress, proliferation stress, cellular senescence, and low proliferative potential. These findings suggest that patients with a history of VTD are ECFC-ECs dysfunctional that could be associated to permanent risk for new thrombotic events.

  13. Origin and Proliferation of Multiple-Drug Resistance in Bacterial Pathogens

    PubMed Central

    Chang, Hsiao-Han; Cohen, Ted; Grad, Yonatan H.; Hanage, William P.; O'Brien, Thomas F.

    2015-01-01

    SUMMARY Many studies report the high prevalence of multiply drug-resistant (MDR) strains. Because MDR infections are often significantly harder and more expensive to treat, they represent a growing public health threat. However, for different pathogens, different underlying mechanisms are traditionally used to explain these observations, and it is unclear whether each bacterial taxon has its own mechanism(s) for multidrug resistance or whether there are common mechanisms between distantly related pathogens. In this review, we provide a systematic overview of the causes of the excess of MDR infections and define testable predictions made by each hypothetical mechanism, including experimental, epidemiological, population genomic, and other tests of these hypotheses. Better understanding the cause(s) of the excess of MDR is the first step to rational design of more effective interventions to prevent the origin and/or proliferation of MDR. PMID:25652543

  14. Bacterial Proliferation: Keep Dividing and Don't Mind the Gap.

    PubMed

    Laureti, Luisa; Demol, Julien; Fuchs, Robert P; Pagès, Vincent

    2015-12-01

    DNA Damage Tolerance (DDT) mechanisms help dealing with unrepaired DNA lesions that block replication and challenge genome integrity. Previous in vitro studies showed that the bacterial replicase is able to re-prime downstream of a DNA lesion, leaving behind a single-stranded DNA gap. The question remains of what happens to this gap in vivo. Following the insertion of a single lesion in the chromosome of a living cell, we showed that this gap is mostly filled in by Homology Directed Gap Repair in a RecA dependent manner. When cells fail to repair this gap, or when homologous recombination is impaired, cells are still able to divide, leading to the loss of the damaged chromatid, suggesting that bacteria lack a stringent cell division checkpoint mechanism. Hence, at the expense of losing one chromatid, cell survival and proliferation are ensured.

  15. Surface tailored organobentonite enhances bacterial proliferation and phenanthrene biodegradation under cadmium co-contamination.

    PubMed

    Mandal, Asit; Biswas, Bhabananda; Sarkar, Binoy; Patra, Ashok K; Naidu, Ravi

    2016-04-15

    Co-contamination of soil and water with polycyclic aromatic hydrocarbon (PAH) and heavy metals makes biodegradation of the former extremely challenging. Modified clay-modulated microbial degradation provides a novel insight in addressing this issue. This study was conducted to evaluate the growth and phenanthrene degradation performance of Mycobacterium gilvum VF1 in the presence of a palmitic acid (PA)-grafted Arquad® 2HT-75-based organobentonite in cadmium (Cd)-phenanthrene co-contaminated water. The PA-grafted organobentonite (ABP) adsorbed a slightly greater quantity of Cd than bentonite at up to 30mgL(-1) metal concentration, but its highly negative surface charge imparted by carboxylic groups indicated the potential of being a significantly superior adsorbent of Cd at higher metal concentrations. In systems co-contained with Cd (5 and 10mgL(-1)), the Arquad® 2HT-75-modified bentonite (AB) and PA-grafted organobentonite (ABP) resulted in a significantly higher (72-78%) degradation of phenanthrene than bentonite (62%) by the bacterium. The growth and proliferation of bacteria were supported by ABP which not only eliminated Cd toxicity through adsorption but also created a congenial microenvironment for bacterial survival. The macromolecules produced during ABP-bacteria interaction could form a stable clay-bacterial cluster by overcoming the electrostatic repulsion among individual components. Findings of this study provide new insights for designing clay modulated PAH bioremediation technologies in mixed-contaminated water and soil.

  16. SB-RA-2001 Inhibits Bacterial Proliferation by Targeting FtsZ Assembly

    PubMed Central

    2015-01-01

    FtsZ has been recognized as a promising antimicrobial drug target because of its vital role in bacterial cell division. In this work, we found that a taxane SB-RA-2001 inhibited the proliferation of Bacillus subtilis 168 and Mycobacterium smegmatis cells with minimal inhibitory concentrations of 38 and 60 μM, respectively. Cell lengths of these microorganisms increased remarkably in the presence of SB-RA-2001, indicating that it inhibits bacterial cytokinesis. SB-RA-2001 perturbed the formation of the FtsZ ring in B. subtilis 168 cells and also affected the localization of the late cell division protein, DivIVA, at the midcell position. Flow cytometric analysis of the SB-RA-2001-treated cells indicated that the compound did not affect the duplication of DNA in B. subtilis 168 cells. Further, SB-RA-2001 treatment did not affect the localization of the chromosomal partitioning protein, Spo0J, along the two ends of the nucleoids and also had no discernible effect on the nucleoid segregation in B. subtilis 168 cells. The agent also did not appear to perturb the membrane potential of B. subtilis 168 cells. In vitro, SB-RA-2001 bound to FtsZ with modest affinity, promoted the assembly and bundling of FtsZ protofilaments, and reduced the GTPase activity of FtsZ. GTP did not inhibit the binding of SB-RA-2001 to FtsZ, suggesting that it does not bind to the GTP binding site on FtsZ. A computational analysis indicated that SB-RA-2001 binds to FtsZ in the cleft region between the C-terminal domain and helix H7, and the binding site of SB-RA-2001 on FtsZ resembled that of PC190723, a well-characterized inhibitor of FtsZ. The findings collectively suggested that SB-RA-2001 inhibits bacterial proliferation by targeting the assembly dynamics of FtsZ, and this can be exploited further to develop potent FtsZ-targeted antimicrobials. PMID:24749867

  17. SB-RA-2001 inhibits bacterial proliferation by targeting FtsZ assembly.

    PubMed

    Singh, Dipty; Bhattacharya, Anusri; Rai, Ankit; Dhaked, Hemendra Pal Singh; Awasthi, Divya; Ojima, Iwao; Panda, Dulal

    2014-05-13

    FtsZ has been recognized as a promising antimicrobial drug target because of its vital role in bacterial cell division. In this work, we found that a taxane SB-RA-2001 inhibited the proliferation of Bacillus subtilis 168 and Mycobacterium smegmatis cells with minimal inhibitory concentrations of 38 and 60 μM, respectively. Cell lengths of these microorganisms increased remarkably in the presence of SB-RA-2001, indicating that it inhibits bacterial cytokinesis. SB-RA-2001 perturbed the formation of the FtsZ ring in B. subtilis 168 cells and also affected the localization of the late cell division protein, DivIVA, at the midcell position. Flow cytometric analysis of the SB-RA-2001-treated cells indicated that the compound did not affect the duplication of DNA in B. subtilis 168 cells. Further, SB-RA-2001 treatment did not affect the localization of the chromosomal partitioning protein, Spo0J, along the two ends of the nucleoids and also had no discernible effect on the nucleoid segregation in B. subtilis 168 cells. The agent also did not appear to perturb the membrane potential of B. subtilis 168 cells. In vitro, SB-RA-2001 bound to FtsZ with modest affinity, promoted the assembly and bundling of FtsZ protofilaments, and reduced the GTPase activity of FtsZ. GTP did not inhibit the binding of SB-RA-2001 to FtsZ, suggesting that it does not bind to the GTP binding site on FtsZ. A computational analysis indicated that SB-RA-2001 binds to FtsZ in the cleft region between the C-terminal domain and helix H7, and the binding site of SB-RA-2001 on FtsZ resembled that of PC190723, a well-characterized inhibitor of FtsZ. The findings collectively suggested that SB-RA-2001 inhibits bacterial proliferation by targeting the assembly dynamics of FtsZ, and this can be exploited further to develop potent FtsZ-targeted antimicrobials.

  18. Thrombospondin-1 regulates adiposity and metabolic dysfunction in diet-induced obesity enhancing adipose inflammation and stimulating adipocyte proliferation

    PubMed Central

    Kong, Ping; Gonzalez-Quesada, Carlos; Li, Na; Cavalera, Michele; Lee, Dong-Wook

    2013-01-01

    As a typical matricellular protein, thrombospondin (TSP)-1, binds to the structural matrix and regulates cellular behavior by modulating growth factor and cytokine signaling. Obesity and diabetes are associated with marked upregulation of TSP-1 in adipose tissue. We hypothesized that endogenous TSP-1 may play an important role in the pathogenesis of diet-induced obesity and metabolic dysfunction. Accordingly, we examined the effects of TSP-1 gene disruption on weight gain, adiposity, and adipose tissue inflammation in mice receiving a high-fat diet (HFD: 60% fat, 20% carbohydrate) or a high-carbohydrate low-fat diet (HCLFD: 10% fat, 70% carbohydrate). HFD mice had significantly higher TSP-1 expression in perigonadal adipose tissue; TSP-1 was predominantly localized in the adipose interstitium. TSP-1 loss attenuated weight gain and fat accumulation in HFD and HCLFD groups. Compared with corresponding wild-type animals, TSP-1-null mice had decreased insulin levels but exhibited elevated free fatty acid and triglyceride levels, suggesting impaired fatty acid uptake. TSP-1 loss did not affect adipocyte size and had no effect on adipose vascular density. However, TSP-1-null mice exhibited attenuated tumor necrosis factor-α mRNA expression and reduced macrophage infiltration, suggesting a role for TSP-1 in mediating obesity-associated inflammation. In vitro, TSP-1 enhanced proliferation of 3T3-L1 preadipocytes but did not modulate inflammatory cytokine and chemokine synthesis. In conclusion, TSP-1 upregulation contributes to weight gain, adipose growth, and the pathogenesis of metabolic dysfunction. The effects of TSP-1 may involve stimulation of adipocyte proliferation, activation of inflammatory signaling, and facilitated fatty acid uptake by adipocytes. PMID:23757408

  19. Tightening of healing abutments: influence of torque on bacterial proliferation risk, an in vitro investigation.

    PubMed

    Bousquet, Philippe; Bennasar, Isabelle Calas; Tramini, Paul; Jacquemot, Maxime; Cuisinier, Frédéric

    2014-12-01

    Gap at the implant-healing abutment junction can increase the risk of bacterial proliferation. In this study, we determined the leakage at the microgap, and we evaluated hand screwing among clinicians. The torques tested with nitrogen gas flow were 10, 15, 20, and 30 N cm, and 54 clinicians were asked to torque down a healing abutment as for a surgical procedure. There were no significant differences between 10 and 15 N cm, with a total lack of tightness. For 20 and 30 N cm, there was a notable decrease in leakage. The torque achieved by hand was <10 N cm for 61.7% of the clinicians, between 10 and 15 N cm for 29.1%, between 15 and 20 N cm for 8.0%, and between 20 and 25 N cm for 1.2%. There was a significant difference related to the strength of tightening. Under the conditions of our experiment, the gap of connection was reduced with a torque of ≥20 N cm. Only a small portion of the clinicians could obtain these values by hand. Therefore, a dynamometrical manual wrench should be used to minimize the gap during the osseointegration period.

  20. Peroxisome proliferator-activated receptors modulate cardiac dysfunction in diabetic cardiomyopathy.

    PubMed

    Lee, T-I; Kao, Y-H; Chen, Y-C; Huang, J-H; Hsiao, F-C; Chen, Y-J

    2013-06-01

    Cardiovascular disease (CVD) is the leading cause of morbidity and mortality among patients with diabetes mellitus (DM). Chronic inflammation and derangement of myocardial energy and lipid homeostasis are common features of DM. The transcription factors of peroxisome proliferator-activated receptors (PPARs) belong to the nuclear receptor superfamily, which are important in regulating energy and lipid homeostasis. There are three PPAR isoforms, α, γ, and δ, and their roles have been increasingly recognized to be important in CVD. These three isoforms are expressed in the heart and play pivotal roles in myocardial lipid metabolism, as well as glucose and energy homeostasis, and contribute to extra metabolic roles with effects on inflammation and oxidative stress. Moreover, regulation of PPARs may have significant effects on cardiac electrical activity and arrhythmogenesis. This review describes the roles of PPARs and their agonists in DM cardiomyopathy, inflammation, and cardiac electrophysiology. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  1. Telmisartan protects against microvascular dysfunction during myocardial ischemia/reperfusion injury by activation of peroxisome proliferator-activated receptor gamma

    PubMed Central

    2013-01-01

    Background We investigated the potential of telmisartan to improve microvascular dysfunction induced by myocardial ischemia/reperfusion (I/R) injury by activating the peroxisome proliferator-activated receptor gamma (PPARG) pathway. Methods Forty-eight male rabbits were randomly allocated into sham-operated, I/R, GW9662, telmisartan, telmisartan–GW9662, or candesartan groups. Rabbits were anesthetized, and the left anterior descending coronary artery (LAD) was ligated for 60 minutes. Following reperfusion for 6 hours, angiotensin II content of the heart was determined using radioimmunoassay. Myocardial neutrophil accumulation and microvessel cross-sectional area were examined histologically. Myocardial capillaries were examined with transmission electron microscopy. Intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in the myocardium were measured using enzyme-linked immunosorbent assay. Western blot was utilized for investigating the expression of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and PPARG. Results Angiotensin II concentration was significantly increased in all treatment groups compared with the sham-operated group (P < 0.05, all). Accumulation of polymorphonuclear neutrophils was significantly lower, while microvessel cross-sectional area was significantly higher in the telmisartan, telmisartan-GW9662, and candesartan groups compared with the I/R group (P < 0.05). ICAM-1 and VCAM-1 levels were also significantly lower, and correlated with lower NF-κB expression in these groups. The effects were the most significant in the telmisartan group compared with the telmisartan–GW9662 and candesartan groups. Telmisartan significantly increased PPARG protein expression compared with all other groups (P < 0.05, all). Conclusions Except for the typical effects of angiotensin II-receptor blocker, telmisartan improved microvascular dysfunction during myocardial I/R injury via the

  2. Mycobacterium ulcerans infections cause progressive muscle atrophy and dysfunction, and mycolactone impairs satellite cell proliferation.

    PubMed

    Houngbédji, Germain Mabèrou; Bouchard, Patrice; Frenette, Jérôme

    2011-03-01

    Clinical observations from Buruli ulcer (BU) patients in West Africa suggest that severe Mycobacterium ulcerans infections can cause skeletal muscle contracture and atrophy leading to significant impairment in function. In the present study, male mice C57BL/6 were subcutaneously injected with M. ulcerans in proximity to the right biceps muscle, avoiding direct physical contact between the infectious agent and the skeletal muscle. The histological, morphological, and functional properties of the muscles were assessed at different times after the injection. On day 42 postinjection, the isometric tetanic force and the cross-sectional area of the myofibers were reduced by 31% and 29%, respectively, in the proximate-infected muscles relative to the control muscles. The necrotic areas of the proximate-infected muscles had spread to 7% of the total area by day 42 postinjection. However, the number of central nucleated fibers and myogenic regulatory factors (MyoD and myogenin) remained stable and low. Furthermore, Pax-7 expression did not increase significantly in mycolactone-injected muscles, indicating that the satellite cell proliferation is abrogated by the toxin. In addition, the fibrotic area increased progressively during the infection. Lastly, muscle-specific RING finger protein 1 (MuRF-1) and atrogin-1/muscle atrophy F-box protein (atrogin-1/MAFbx), two muscle-specific E3 ubiquitin ligases, were upregulated in the presence of M. ulcerans. These findings confirmed that skeletal muscle is affected in our model of subcutaneous infection with M. ulcerans and that a better understanding of muscle contractures and weakness is essential to develop a therapy to minimize loss of function and promote the autonomy of BU patients.

  3. The FBPase Encoding Gene glpX Is Required for Gluconeogenesis, Bacterial Proliferation and Division In Vivo of Mycobacterium marinum

    PubMed Central

    Lyu, Liangdong; Wang, Chuan; Li, Yang; Gao, Qian; Yang, Chen

    2016-01-01

    Lipids have been identified as important carbon sources for Mycobacterium tuberculosis (Mtb) to utilize in vivo. Thus gluconeogenesis bears a key role for Mtb to survive and replicate in host. A rate-limiting enzyme of gluconeogenesis, fructose 1, 6-bisphosphatase (FBPase) is encoded by the gene glpX. The functions of glpX were studied in M. marinum, a closely related species to Mtb. The glpX deletion strain (ΔglpX) displayed altered gluconeogenesis, attenuated virulence, and altered bacterial proliferation. Metabolic profiles indicate an accumulation of the FBPase substrate, fructose 1, 6-bisphosphate (FBP) and altered gluconeogenic flux when ΔglpX is cultivated in a gluconeogenic carbon substrate, acetate. In both macrophages and zebrafish, the proliferation of ΔglpX was halted, resulting in dramatically attenuated virulence. Intracellular ΔglpX exhibited an elongated morphology, which was also observed when ΔglpX was grown in a gluconeogenic carbon source. This elongated morphology is also supported by the observation of unseparated multi-nucleoid cell, indicating that a complete mycobacterial division in vivo is correlated with intact gluconeogenesis. Together, our results indicate that glpX has essential functions in gluconeogenesis, and plays an indispensable role in bacterial proliferation in vivo and virulence of M. marinum. PMID:27233038

  4. Tagging Frogs with Passive Integrated Transponders Causes Disruption of the Cutaneous Bacterial Community and Proliferation of Opportunistic Fungi

    PubMed Central

    Garcia, Gerardo; Fidgett, Andrea L.; Preziosi, Richard F.

    2014-01-01

    Symbiotic bacterial communities play a key role in protecting amphibians from infectious diseases including chytridiomycosis, caused by the pathogenic fungus Batrachochytrium dendrobatidis. Events that lead to the disruption of the bacterial community may have implications for the susceptibility of amphibians to such diseases. Amphibians are often marked both in the wild and in captivity for a variety of reasons, and although existing literature indicates that marking techniques have few negative effects, the response of cutaneous microbial communities has not yet been investigated. Here we determine the effects of passive integrated transponder (PIT) tagging on culturable cutaneous microbial communities of captive Morelet's tree frogs (Agalychnis moreletii) and assess the isolated bacterial strains for anti-B. dendrobatidis activity in vitro. We find that PIT tagging causes a major disruption to the bacterial community associated with the skin of frogs (∼12-fold increase in abundance), as well as a concurrent proliferation in resident fungi (up to ∼200-fold increase). Handling also caused a disruption the bacterial community, although to a lesser extent than PIT tagging. However, the effects of both tagging and handling were temporary, and after 2 weeks, the bacterial communities were similar to their original compositions. We also identify two bacterial strains that inhibit B. dendrobatidis, one of which increased in abundance on PIT-tagged frogs at 1 day postmarking, while the other was unaffected. These results show that PIT tagging has previously unobserved consequences for cutaneous microbial communities of frogs and may be particularly relevant for studies that intend to use PIT tagging to identify individuals involved in trials to develop probiotic treatments. PMID:24878599

  5. Bacterial factors exploit eukaryotic Rho GTPase signaling cascades to promote invasion and proliferation within their host

    PubMed Central

    Popoff, Michel R

    2014-01-01

    Actin cytoskeleton is a main target of many bacterial pathogens. Among the multiple regulation steps of the actin cytoskeleton, bacterial factors interact preferentially with RhoGTPases. Pathogens secrete either toxins which diffuse in the surrounding environment, or directly inject virulence factors into target cells. Bacterial toxins, which interfere with RhoGTPases, and to some extent with RasGTPases, catalyze a covalent modification (ADPribosylation, glucosylation, deamidation, adenylation, proteolysis) blocking these molecules in their active or inactive state, resulting in alteration of epithelial and/or endothelial barriers, which contributes to dissemination of bacteria in the host. Injected bacterial virulence factors preferentially manipulate the RhoGTPase signaling cascade by mimicry of eukaryotic regulatory proteins leading to local actin cytoskeleton rearrangement, which mediates bacterial entry into host cells or in contrast escape to phagocytosis and immune defense. Invasive bacteria can also manipulate RhoGTPase signaling through recognition and stimulation of cell surface receptor(s). Changes in RhoGTPase activation state is sensed by the innate immunity pathways and allows the host cell to adapt an appropriate defense response. PMID:25203748

  6. Potential mechanisms underlying the acute lung dysfunction and bacterial extrapulmonary dissemination during Burkholderia cenocepacia respiratory infection

    PubMed Central

    2010-01-01

    Background Burkholderia cenocepacia, an opportunistic pathogen that causes lung infections in cystic fibrosis (CF) patients, is associated with rapid and usually fatal lung deterioration due to necrotizing pneumonia and sepsis, a condition known as cepacia syndrome. The key bacterial determinants associated with this poor clinical outcome in CF patients are not clear. In this study, the cytotoxicity and procoagulant activity of B. cenocepacia from the ET-12 lineage, that has been linked to the cepacia syndrome, and four clinical isolates recovered from CF patients with mild clinical courses were analysed in both in vitro and in vivo assays. Methods B. cenocepacia-infected BEAS-2B epithelial respiratory cells were used to investigate the bacterial cytotoxicity assessed by the flow cytometric detection of cell staining with propidium iodide. Bacteria-induced procoagulant activity in cell cultures was assessed by a colorimetric assay and by the flow cytometric detection of tissue factor (TF)-bearing microparticles in cell culture supernatants. Bronchoalveolar lavage fluids (BALF) from intratracheally infected mice were assessed for bacterial proinflammatory and procoagulant activities as well as for bacterial cytotoxicity, by the detection of released lactate dehydrogenase. Results ET-12 was significantly more cytotoxic to cell cultures but clinical isolates Cl-2, Cl-3 and Cl-4 exhibited also a cytotoxic profile. ET-12 and CI-2 were similarly able to generate a TF-dependent procoagulant environment in cell culture supernatant and to enhance the release of TF-bearing microparticles from infected cells. In the in vivo assay, all bacterial isolates disseminated from the mice lungs, but Cl-2 and Cl-4 exhibited the highest rates of recovery from mice livers. Interestingly, Cl-2 and Cl-4, together with ET-12, exhibited the highest cytotoxicity. All bacteria were similarly capable of generating a procoagulant and inflammatory environment in animal lungs. Conclusion B

  7. Potential mechanisms underlying the acute lung dysfunction and bacterial extrapulmonary dissemination during Burkholderia cenocepacia respiratory infection.

    PubMed

    Cunha, Luiz G; Assis, Maria-Cristina; Machado, Gloria-Beatriz; Assef, Ana P; Marques, Elizabeth A; Leão, Robson S; Saliba, Alessandra M; Plotkowski, Maria-Cristina

    2010-01-18

    Burkholderia cenocepacia, an opportunistic pathogen that causes lung infections in cystic fibrosis (CF) patients, is associated with rapid and usually fatal lung deterioration due to necrotizing pneumonia and sepsis, a condition known as cepacia syndrome. The key bacterial determinants associated with this poor clinical outcome in CF patients are not clear. In this study, the cytotoxicity and procoagulant activity of B. cenocepacia from the ET-12 lineage, that has been linked to the cepacia syndrome, and four clinical isolates recovered from CF patients with mild clinical courses were analysed in both in vitro and in vivo assays. B. cenocepacia-infected BEAS-2B epithelial respiratory cells were used to investigate the bacterial cytotoxicity assessed by the flow cytometric detection of cell staining with propidium iodide. Bacteria-induced procoagulant activity in cell cultures was assessed by a colorimetric assay and by the flow cytometric detection of tissue factor (TF)-bearing microparticles in cell culture supernatants. Bronchoalveolar lavage fluids (BALF) from intratracheally infected mice were assessed for bacterial proinflammatory and procoagulant activities as well as for bacterial cytotoxicity, by the detection of released lactate dehydrogenase. ET-12 was significantly more cytotoxic to cell cultures but clinical isolates Cl-2, Cl-3 and Cl-4 exhibited also a cytotoxic profile. ET-12 and CI-2 were similarly able to generate a TF-dependent procoagulant environment in cell culture supernatant and to enhance the release of TF-bearing microparticles from infected cells. In the in vivo assay, all bacterial isolates disseminated from the mice lungs, but Cl-2 and Cl-4 exhibited the highest rates of recovery from mice livers. Interestingly, Cl-2 and Cl-4, together with ET-12, exhibited the highest cytotoxicity. All bacteria were similarly capable of generating a procoagulant and inflammatory environment in animal lungs. B. cenocepacia were shown to exhibit cytotoxic

  8. AMG 900, pan-Aurora kinase inhibitor, preferentially inhibits the proliferation of breast cancer cell lines with dysfunctional p53.

    PubMed

    Kalous, Ondrej; Conklin, Dylan; Desai, Amrita J; Dering, Judy; Goldstein, Jennifer; Ginther, Charles; Anderson, Lee; Lu, Ming; Kolarova, Teodora; Eckardt, Mark A; Langerød, Anita; Børresen-Dale, Anne-Lise; Slamon, Dennis J; Finn, Richard S

    2013-10-01

    Aurora kinases play important roles in cell division and are frequently overexpressed in human cancer. AMG 900 is a novel pan-Aurora kinase inhibitor currently being tested in Phase I clinical trials. We aimed to evaluate the in vitro activity of AMG 900 in a panel of 44 human breast cancer and immortalized cell lines and identify predictors of response. AMG 900 inhibited proliferation at low nanomolar concentrations in all cell lines tested. Response was further classified based on the induction of lethality. 25 cell lines were classified as highly sensitive (lethality at 10 nM of AMG 900 >10 %), 19 cell lines as less sensitive to AMG 900 (lethality at 10 nM of AMG 900 <10 %). Traditional molecular subtypes of breast cancer did not predict for this differential response. There was a weak association between AURKA amplification and response to AMG 900 (response ratio = 2.53, p = 0.09). mRNA expression levels of AURKA, AURKB, and AURKC and baseline protein levels of Aurora kinases A and B did not significantly associate with response. Cell lines with TP53 loss of function mutations (RR = 1.86, p = 0.004) and low baseline p21 protein levels (RR = 2.28, p = 0.0004) were far more likely to be classified as highly sensitive to AMG 900. AMG 900 induced p53 and p21 protein expression in cell lines with wt TP53. AMG 900 caused the accumulation of cells with >4 N DNA content in a majority of cell lines independently of sensitivity and p53 status. AMG 900 induced more pronounced apoptosis in highly sensitive p53-dysfunctional cell lines. We have found that AMG 900 is highly active in breast cancer cell lines and that TP53 loss of function mutations as well as low baseline expression of p21 protein predict strongly for increased sensitivity to this compound in vitro.

  9. An Extracellular Bacterial Pathogen Modulates Host Metabolism to Regulate its Own Sensing and Proliferation

    PubMed Central

    Baruch, Moshe; Belotserkovsky, Ilia; Hertzog, Baruch B.; Ravins, Miriam; Dov, Eran; McIver, Kevin S.; Le Breton, Yoann S.; Zhou, Yiting; Youting, Catherine Cheng; Hanski, Emanuel

    2014-01-01

    SUMMARY Successful infection depends on the ability of the pathogen to gain nutrients from the host. The extracellular pathogenic bacterium group A Streptococcus (GAS) causes a vast array of human diseases. By using the quorum sensing sil system as a reporter, we found that during adherence to host cells GAS delivers streptolysin toxins creating endoplasmic reticulum stress. This in turn, increases asparagine (ASN) synthetase expression and the production of ASN. The released ASN is sensed by the bacteria altering the expression of ~17% of GAS genes of which about 1/3 are dependent on the two-component system TrxSR. The expression of the streptolysin toxins is strongly upregulated whereas genes linked to proliferation are downregulated in ASN absence. Asparaginase a widely used chemotherapeutic agent, arrests GAS growth in human blood and blocks GAS proliferation in a mouse model of human bacteremia. These results delineate a pathogenic pathway and propose a new therapeutic strategy against GAS infections. PMID:24439371

  10. Reduced bacterial growth and increased osteoblast proliferation on titanium with a nanophase TiO2 surface treatment

    PubMed Central

    Bhardwaj, Garima; Webster, Thomas J

    2017-01-01

    Background The attachment and initial growth of bacteria on an implant surface dictates the progression of infection. Treatment often requires aggressive antibiotic use, which does not always work. To overcome the difficulties faced in systemic and local antibiotic delivery, scientists have forayed into using alternative techniques, which includes implant surface modifications that prevent initial bacterial adhesion, foreign body formation, and may offer a controlled inflammatory response. Objective The current study focused on using electrophoretic deposition to treat titanium with a nanophase titanium dioxide surface texture to reduce bacterial adhesion and growth. Two distinct nanotopographies were analyzed, Ti-160, an antimicrobial surface designed to greatly reduce bacterial colonization, and Ti-120, an antimicrobial surface with a topography that upregulates osteoblast activity while reducing bacterial colonization; the number following Ti in the nomenclature represents the atomic force microscopy root-mean-square roughness value in nanometers. Results There was a 95.6% reduction in Staphylococcus aureus (gram-positive bacteria) for the Ti-160-treated surfaces compared to the untreated titanium alloy controls. There was a 90.2% reduction in Pseudomonas aeruginosa (gram-negative bacteria) on Ti-160-treated surfaces compared to controls. For ampicillin-resistant Escherichia coli, there was an 81.1% reduction on the Ti-160-treated surfaces compared to controls. Similarly for surfaces treated with Ti-120, there was an 86.8% reduction in S. aureus, an 82.1% reduction in P. aeruginosa, and a 48.6% reduction in ampicillin-resistant E. coli. The Ti-120 also displayed a 120.7% increase at day 3 and a 168.7% increase at day 5 of osteoblast proliferation over standard titanium alloy control surfaces. Conclusion Compared to untreated surfaces, Ti-160-treated titanium surfaces demonstrated a statistically significant 1 log reduction in S. aureus and P. aeruginosa, whereas

  11. Nanogrooves and keratin nanofibers on titanium surfaces aimed at driving gingival fibroblasts alignment and proliferation without increasing bacterial adhesion.

    PubMed

    Ferraris, S; Truffa Giachet, F; Miola, M; Bertone, E; Varesano, A; Vineis, C; Cochis, A; Sorrentino, R; Rimondini, L; Spriano, S

    2017-07-01

    Periimplantitis and epithelial downgrowth are nowadays the main conditions associated to transmucosal dental implants. Gingival fibroblasts can play an important role in periimplantitis because they are the promoters of the inflammatory process and eventual tissue homeostasis and destruction. Moreover, the related inflammatory state is commonly driven also to counteract bacteria implants colonization. In the present research, a new technology based on mechanically produced nanogrooves (0.1-0.2μm) and keratin nanofibers deposited by electrospinning has been proposed in order to obtain titanium surfaces able to drive gingival fibroblasts alignment and proliferation without increasing bacterial adhesion. The prepared surfaces have been characterized for their morphology (FESEM), chemical composition (FTIR, XPS), surface charge (zeta potential) and wettability (contact angle). Afterwards, their performances in terms of cells (human primary gingival fibroblasts) and bacteria (Staphylococcus aureus) adhesion were compared to mirror-like polished titanium surfaces. Results revealed that gingival fibroblasts viability was not negatively affected by the applied surface roughness or by keratin nanofibers. On the opposite, cells adhesion and spread were strongly influenced by surface roughness revealing a significant cell orientation along the produced nanogrooves. However, the keratin influence was clearly predominant with respect to surface topography, thus leading to increased cells proliferation on the surfaces with nanofibers, disregarding the presence of the surfaces grooves. Moreover, nor nanogrooves nor keratin nanofibers increase bacterial biofilm adhesion in comparison with mirror polished surfaces. Thus, the present research represents a promising innovative strategy and technology for a surface modification finalized to match the main requirements for transmucosal dental implants. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Aerosol treatment with MNEI suppresses bacterial proliferation in a model of chronic Pseudomonas aeruginosa lung infection.

    PubMed

    Woods, Donald E; Cantin, André; Cooley, Jessica; Kenney, Dianne M; Remold-O'Donnell, Eileen

    2005-02-01

    Neutrophil elastase is present at high levels in airway fluid of patients with cystic fibrosis (CF), and is responsible for considerable inflammatory damage. Human monocyte/neutrophil elastase inhibitor (MNEI), a 42-kDa serpin protein, is an effective inhibitor of neutrophil elastase, cathepsin G, and proteinase-3, related proteases released from inflammatory neutrophils. We hypothesized that recombinant MNEI would reduce inflammatory damage and enhance bacterial clearance from the lung in an animal model of chronic Pseudomonas aeruginosa infection. In vitro studies showed that MNEI causes dose-dependent inhibition of the activity of rat neutrophil elastase. Recombinant MNEI was administered daily by aerosolization to rats previously inoculated with agar beads containing P. aeruginosa to initiate chronic infection. Administered MNEI was partially recovered in lavage fluid of treated rats as a 66-kDa complex with protease indicative of in vivo inhibition of elastase or a related protease. Aerosol treatment with MNEI significantly decreased the extent of inflammatory injury, quantified as the histopathology score. MNEI, which had no bactericidal effect on P. aeruginosa in vitro, significantly enhanced clearance of bacteria from infected rat lungs. The reduction of histopathology scores and enhancement of bacterial killing were evident 6 hr after a single aerosol treatment with MNEI. These findings indicate an important function of MNEI in protecting innate antimicrobial defense. Similar results were previously obtained for aerosolized prolastin (alpha1-antitrypsin), indicating that enhanced bacterial clearance by MNEI is due to inhibition of neutrophil protease. These findings demonstrate the value of this nonantibiotic protease inhibitor as an adjunct for the treatment and prevention of the infection component of CF lung disease.

  13. Glutamine deamidation and dysfunction of ubiquitin/NEDD8 induced by a bacterial effector family.

    PubMed

    Cui, Jixin; Yao, Qing; Li, Shan; Ding, Xiaojun; Lu, Qiuhe; Mao, Haibin; Liu, Liping; Zheng, Ning; Chen, She; Shao, Feng

    2010-09-03

    A family of bacterial effectors including Cif homolog from Burkholderia pseudomallei (CHBP) and Cif from Enteropathogenic Escherichia coli (EPEC) adopt a functionally important papain-like hydrolytic fold. We show here that CHBP was a potent inhibitor of the eukaryotic ubiquitination pathway. CHBP acted as a deamidase that specifically and efficiently deamidated Gln40 in ubiquitin and ubiquitin-like protein NEDD8 both in vitro and during Burkholderia infection. Deamidated ubiquitin was impaired in supporting ubiquitin-chain synthesis. Cif selectively deamidated NEDD8, which abolished the activity of neddylated Cullin-RING ubiquitin ligases (CRLs). Ubiquitination and ubiquitin-dependent degradation of multiple CRL substrates were impaired by Cif in EPEC-infected cells. Mutations of substrate-contacting residues in Cif abolished or attenuated EPEC-induced cytopathic phenotypes of cell cycle arrest and actin stress fiber formation.

  14. Fluoroquinolone–macrolide combination therapy for chronic bacterial prostatitis: retrospective analysis of pathogen eradication rates, inflammatory findings and sexual dysfunction

    PubMed Central

    Magri, Vittorio; Montanari, Emanuele; Škerk, Višnja; Markotić, Alemka; Marras, Emanuela; Restelli, Antonella; Naber, Kurt G; Perletti, Gianpaolo

    2011-01-01

    We previously demonstrated the safety and efficacy of fluoroquinolone–macrolide combination therapy in category II chronic bacterial prostatitis (CBP). The aim of this study is to retrospectively compare the microbiological and clinical findings of two treatment schemes for CBP based on the combination of azithromycin (500 mg, thrice-weekly) with a once-daily 500- or 750-mg dose of ciprofloxacin (Cipro-500 or Cipro-750 cohort, respectively). Combined administration of azithromycin (1500 mg week−1) with ciprofloxacin at the rate of 750 mg day−1 for 4 weeks rather than at 500 mg day−1 for 6 weeks increased the eradication rates from 62.35% to 77.32% and the total bacteriological success from 71.76% to 85.57%. A significant decrease in pain and voiding signs/symptoms and a significant reduction in inflammatory leukocyte counts and serum prostate-specific antigen (PSA) were sustained throughout an 18-month follow-up period in both groups. Ejaculatory pain, haemospermia and premature ejaculation were significantly attenuated on microbiological eradication in both groups, but the latter subsided more promptly in the Cipro-750 cohort. In total, 59 Cipro-750 patients showed mild-to-severe erectile dysfunction (ED) at baseline, while 22 patients had no ED on microbiological eradication and throughout the follow-up period. In conclusion fluoroquinolone–macrolide therapy resulted in pathogen eradication and CBP symptom attenuation, including pain, voiding disturbances and sexual dysfunction. A once-daily 750-mg dose of ciprofloxacin for 4 weeks showed enhanced eradication rates and lower inflammatory white blood cell counts compared to the 500-mg dose for 6 weeks. Our results are open to further prospective validation. PMID:21765442

  15. BT-benzo-29 inhibits bacterial cell proliferation by perturbing FtsZ assembly.

    PubMed

    Ray, Shashikant; Jindal, Bhavya; Kunal, Kishore; Surolia, Avadhesha; Panda, Dulal

    2015-10-01

    We have identified a potent antibacterial agent N-(4-sec-butylphenyl)-2-(thiophen-2-yl)-1H-benzo[d]imidazole-4-carboxamide (BT-benzo-29) from a library of benzimidazole derivatives that stalled bacterial division by inhibiting FtsZ assembly. A short (5 min) exposure of BT-benzo-29 disassembled the cytokinetic Z-ring in Bacillus subtilis cells without affecting the cell length and nucleoids. BT-benzo-29 also perturbed the localization of early and late division proteins such as FtsA, ZapA and SepF at the mid-cell. Further, BT-benzo-29 bound to FtsZ with a dissociation constant of 24 ± 3 μm and inhibited the assembly and GTPase activity of purified FtsZ. A docking analysis suggested that BT-benzo-29 may bind to FtsZ at the C-terminal domain near the T7 loop. BT-benzo-29 displayed significantly weaker inhibitory effects on the assembly and GTPase activity of two mutants (L272A and V275A) of FtsZ supporting the prediction of the docking analysis. Further, BT-benzo-29 did not appear to inhibit DNA duplication and nucleoid segregation and it did not perturb the membrane potential of B. subtilis cells. The results suggested that BT-benzo-29 exerts its potent antibacterial activity by inhibiting FtsZ assembly. Interestingly, BT-benzo-29 did not affect the membrane integrity of mammalian red blood cells. BT-benzo-29 bound to tubulin with a much weaker affinity than FtsZ and exerted significantly weaker effects on mammalian cells than on the bacterial cells indicating that the compound may have a strong antibacterial potential.

  16. Multifunctional CuS nanocrystals for inhibiting both osteosarcoma proliferation and bacterial infection by photothermal therapy

    NASA Astrophysics Data System (ADS)

    Hu, Xiaoming; Li, Lihua; Lu, Yao; Liu, Cong; Lei, Yangqing; Zhang, Chengcheng; Yin, Qingshui; Zhang, Yu

    2017-09-01

    Photothermal therapy (PTT) has attracted great attention in cancer therapy because of high efficiency and low side effect. The semiconductors have been proved to be ideal photothermal agents in the past years. Herein, we synthesized a novel hexahedron structure of polyvinyl pyrrolidone (PVP) coating CuS nanocrystals (NCs) by a facile hydrothermal method. The synthesized CuS NCs (150 nm for average length of edge and 125 nm for length of width) have good biocompatibility due to their PVP coating and strong absorption in the near infrared region. Moreover, the CuS NCs exhibit high photothermal conversion efficiency as well as good antibacterial effect. Notably, the proliferation of osteosarcoma cancer cells can be efficiently inhibited both in vitro and in vivo by the fatal heat with very low concentration of CuS NCs under the near infrared ray at a power density of 0.5 W/cm2. Therefore, the CuS-PVP NCs have great potential to work as an ideal photothermal and antibacterial agent in clinical applications.

  17. Is Alveolar Macrophage Phagocytic Dysfunction in Children With Protracted Bacterial Bronchitis a Forerunner to Bronchiectasis?

    PubMed

    Hodge, Sandra; Upham, John W; Pizzutto, Susan; Petsky, Helen L; Yerkovich, Stephanie; Baines, Katherine J; Gibson, Peter; Simpson, Jodie L; Buntain, Helen; Chen, Alice C H; Hodge, Greg; Chang, Anne B

    2016-02-01

    Children with recurrent protracted bacterial bronchitis (PBB) and bronchiectasis share common features, and PBB is likely a forerunner to bronchiectasis. Both diseases are associated with neutrophilic inflammation and frequent isolation of potentially pathogenic microorganisms, including nontypeable Haemophilus influenzae (NTHi), from the lower airway. Defective alveolar macrophage phagocytosis of apoptotic bronchial epithelial cells (efferocytosis), as found in other chronic lung diseases, may also contribute to tissue damage and neutrophil persistence. Thus, in children with bronchiectasis or PBB and in control subjects, we quantified the phagocytosis of airway apoptotic cells and NTHi by alveolar macrophages and related the phagocytic capacity to clinical and airway inflammation. Children with bronchiectasis (n = 55) or PBB (n = 13) and control subjects (n = 13) were recruited. Alveolar macrophage phagocytosis, efferocytosis, and expression of phagocytic scavenger receptors were assessed by flow cytometry. Bronchoalveolar lavage fluid interleukin (IL) 1β was measured by enzyme-linked immunosorbent assay. For children with PBB or bronchiectasis, macrophage phagocytic capacity was significantly lower than for control subjects (P = .003 and P < .001 for efferocytosis and P = .041 and P = .004 for phagocytosis of NTHi; PBB and bronchiectasis, respectively); median phagocytosis of NTHi for the groups was as follows: bronchiectasis, 13.7% (interquartile range [IQR], 11%-16%); PBB, 16% (IQR, 11%-16%); control subjects, 19.0% (IQR, 13%-21%); and median efferocytosis for the groups was as follows: bronchiectasis, 14.1% (IQR, 10%-16%); PBB, 16.2% (IQR, 14%-17%); control subjects, 18.1% (IQR, 16%-21%). Mannose receptor expression was significantly reduced in the bronchiectasis group (P = .019), and IL-1β increased in both bronchiectasis and PBB groups vs control subjects. A reduced alveolar macrophage phagocytic host response to apoptotic cells or NTHi may contribute to

  18. Heteroclitic Peptides Increase Proliferation and Reduce Evidence of Human Immunodeficiency Virus-Specific CD8⁺ T Cell Dysfunction.

    PubMed

    Adegoke, Adeolu; Gladney, Krista; Gallant, Maureen; Grant, Michael

    2015-10-01

    Human immunodeficiency virus (HIV)-specific CD8(+) T cell dysfunction parallels disease progression; therefore, restoring potent HIV-specific CD8(+) T cell responses is a key therapeutic goal. Certain CD8(+) T cell peptide epitope variants, termed heteroclitic, enhance cytokine production by the HIV-specific CD8(+) T cells of some individuals. In this study, we investigated whether heteroclitic peptides that enhance cytokine production by HIV-specific CD8(+) T cells also reduce functional and phenotypic evidence of HIV-specific CD8(+) T cell exhaustion in those instances. Twenty-four variant peptides of human histocompatibility-linked leukocyte antigen (HLA)-A2-restricted reference HIV peptide epitopes designated as A2-7; Nef 83→91, A2-8; Nef 135→143, A2-Gag; Gag 77→85 and A2-9; Gag 433→440 were synthesized with conservative and semiconservative amino acid substitutions at positions 3, 5, and 7 or 3, 5, and 8 of Gag 433→440. Variants that enhanced interferon-gamma (IFN-γ) and/or interleukin-2 (IL-2) production in enzyme-linked immunospot assays (29 cases overall) were subsequently tested by 7-day in vitro peptide stimulation for their effects on HIV-specific CD8(+) T cell proliferation and programmed death-1 (PD-1) expression. Heteroclitic variants enhanced HIV-specific CD8(+) T cell proliferation by >20% in 13/29 cases tested, reduced PD-1 expression on proliferating cells by 15-50% in 10 cases, and reduced PD-1 expression on proliferating cells by >50% in 3 cases. In five cases, the same heteroclitic peptide increased proliferation by >20% and reduced PD-1 expression by >15%. These data demonstrate that heteroclitic peptides can alter the magnitude and character of HIV-specific CD8(+) cell responses relative to reference peptides and may have a unique immunotherapeutic value in therapeutic vaccines.

  19. Mycobacterium tuberculosis dysregulates MMP/TIMP balance to drive rapid cavitation and unrestrained bacterial proliferation.

    PubMed

    Kübler, André; Luna, Brian; Larsson, Christer; Ammerman, Nicole C; Andrade, Bruno B; Orandle, Marlene; Bock, Kevin W; Xu, Ziyue; Bagci, Ulas; Mollura, Daniel J; Marshall, John; Burns, Jay; Winglee, Kathryn; Ahidjo, Bintou Ahmadou; Cheung, Laurene S; Klunk, Mariah; Jain, Sanjay K; Kumar, Nathella Pavan; Babu, Subash; Sher, Alan; Friedland, Jon S; Elkington, Paul T G; Bishai, William R

    2015-02-01

    Active tuberculosis (TB) often presents with advanced pulmonary disease, including irreversible lung damage and cavities. Cavitary pathology contributes to antibiotic failure, transmission, morbidity and mortality. Matrix metalloproteinases (MMPs), in particular MMP-1, are implicated in TB pathogenesis. We explored the mechanisms relating MMP/TIMP imbalance to cavity formation in a modified rabbit model of cavitary TB. Our model resulted in consistent progression of consolidation to human-like cavities (100% by day 28), with resultant bacillary burdens (>10(7) CFU/g) far greater than those found in matched granulomatous tissue (10(5) CFU/g). Using a novel, breath-hold computed tomography (CT) scanning and image analysis protocol, we showed that cavities developed rapidly from areas of densely consolidated tissue. Radiological change correlated with a decrease in functional lung tissue, as estimated by changes in lung density during controlled pulmonary expansion (R(2)  = 0.6356, p < 0.0001). We demonstrated that the expression of interstitial collagenase (MMP-1) was specifically greater in cavitary compared to granulomatous lesions (p < 0.01), and that TIMP-3 significantly decreased at the cavity surface. Our findings demonstrated that an MMP-1/TIMP imbalance is associated with the progression of consolidated regions to cavities containing very high bacterial burdens. Our model provided mechanistic insight, correlating with human disease at the pathological, microbiological and molecular levels. It also provided a strategy to investigate therapeutics in the context of complex TB pathology. We used these findings to predict a MMP/TIMP balance in active TB and confirmed this in human plasma, revealing the potential of MMP/TIMP levels as key components of a diagnostic matrix aimed at distinguishing active from latent TB (PPV = 92.9%, 95% CI 66.1-99.8%, NPV = 85.6%; 95% CI 77.0-91.9%).

  20. Mycobacterium tuberculosis dysregulates MMP/TIMP balance to drive rapid cavitation and unrestrained bacterial proliferation

    PubMed Central

    Kübler, André; Luna, Brian; Larsson, Christer; Ammerman, Nicole C.; Andrade, Bruno B.; Orandle, Marlene; Bock, Kevin W.; Xu, Ziyue; Bagci, Ulas; Molura, Daniel J.; Marshall, John; Burns, Jay; Winglee, Kathryn; Ahidjo, Bintou Ahmadou; Cheung, Laurene S.; Klunk, Mariah; Jain, Sanjay K.; Kumar, Nathella Pavan; Babu, Subash; Sher, Alan; Friedland, Jon S.; Elkington, Paul T. G.; Bishai, William R.

    2014-01-01

    Active tuberculosis (TB) often presents with advanced pulmonary disease, including irreversible lung damage and cavities. Cavitary pathology contributes to antibiotic failure, transmission, morbidity and mortality. Matrix metalloproteinases (MMPs), in particular MMP-1 are implicated in TB pathogenesis. We explored the mechanisms relating MMP/TIMP imbalance to cavity formation in a modified rabbit model of cavitary TB. Our model results in consistent progression of consolidation to human-like cavities (100% by day 28) with resultant bacillary burdens (>107 CFU/g) far greater than those found in matched granulomatous tissue (105 CFU/g). Using a novel, breath-hold computerized tomography scanning and image analysis protocol. We show that cavities develop rapidly from areas of densely consolidated tissue. Radiological change correlated with a decrease in functional lung tissue as estimated by changes in lung density during controlled pulmonary expansion (R2=0.6356, p<0.0001). We demonstrated that the expression of interstitial collagenase (MMP-1) is specifically greater in cavitary compared to granulomatous lesions (p<0.01), and that TIMP-3 significantly decreases at the cavity surface. Our findings demonstrate that an MMP-1/TIMP imbalance, is associated with the progression of consolidated regions to cavities containing very high bacterial burdens. Our model provided mechanistic insight, correlating with human disease at the pathological, microbiological and molecular levels,. It also provides a strategy to investigate therapeutics in the context of complex TB pathology. We used these findings to predict a MMP/TIMP balance in active TB; and confirmed this in human plasma, revealing the potential of MMP/TIMP levels as key components of a diagnostic matrix aimed at distinguishing active from latent TB (PPV=92.9%; 95%CI 66.1–99.8%, NPV=85.6%; 95%CI 77.0–91.9%). PMID:25186281

  1. Ileocecal valve dysfunction in small intestinal bacterial overgrowth: A pilot study

    PubMed Central

    Miller, Larry S; Vegesna, Anil K; Sampath, Aiswerya Madanam; Prabhu, Shital; Kotapati, Sesha Krishna; Makipour, Kian

    2012-01-01

    AIM: To explore whether patients with a defective ileocecal valve (ICV)/cecal distension reflex have small intestinal bacterial overgrowth. METHODS: Using a colonoscope, under conscious sedation, the ICV was intubated and the colonoscope was placed within the terminal ileum (TI). A manometry catheter with 4 pressure channels, spaced 1 cm apart, was passed through the biopsy channel of the colonoscope into the TI. The colonoscope was slowly withdrawn from the TI while the manometry catheter was advanced. The catheter was placed across the ICV so that at least one pressure port was within the TI, ICV and the cecum respectively. Pressures were continuously measured during air insufflation into the cecum, under direct endoscopic visualization, in 19 volunteers. Air was insufflated to a maximum of 40 mmHg to prevent barotrauma. All subjects underwent lactulose breath testing one month after the colonoscopy. The results of the breath tests were compared with the results of the pressures within the ICV during air insufflation. RESULTS: Nineteen subjects underwent colonoscopy with measurements of the ICV pressures after intubation of the ICV with a colonoscope. Initial baseline readings showed no statistical difference in the pressures of the TI and ICV, between subjects with positive lactulose breath tests and normal lactulose breath tests. The average peak ICV pressure during air insufflation into the cecum in subjects with normal lactulose breath tests was significantly higher than cecal pressures during air insufflation (49.33 ± 7.99 mmHg vs 16.40 ± 2.14 mmHg, P = 0.0011). The average percentage difference of the area under the pressure curve of the ICV from the cecum during air insufflations in subjects with normal lactulose breath tests was significantly higher (280.72% ± 43.29% vs 100% ± 0%, P = 0.0006). The average peak ICV pressure during air insufflation into the cecum in subjects with positive lactulose breath tests was not significantly different than cecal

  2. TRF2 dysfunction elicits DNA damage responses associated with senescence in proliferating neural cells and differentiation of neurons.

    PubMed

    Zhang, Peisu; Furukawa, Katsutoshi; Opresko, Patricia L; Xu, Xiangru; Bohr, Vilhelm A; Mattson, Mark P

    2006-04-01

    Telomeres are specialized structures at the ends of chromosomes that consist of tandem repeats of the DNA sequence TTAGGG and several proteins that protect the DNA and regulate the plasticity of the telomeres. The telomere-associated protein TRF2 (telomeric repeat binding factor 2) is critical for the control of telomere structure and function; TRF2 dysfunction results in the exposure of the telomere ends and activation of ATM (ataxia telangiectasin mutated)-mediated DNA damage response. Recent findings suggest that telomere attrition can cause senescence or apoptosis of mitotic cells, but the function of telomeres in differentiated neurons is unknown. Here, we examined the impact of telomere dysfunction via TRF2 inhibition in neurons (primary embryonic hippocampal neurons) and mitotic neural cells (astrocytes and neuroblastoma cells). We demonstrate that telomere dysfunction induced by adenovirus-mediated expression of dominant-negative TRF2 (DN-TRF2) triggers a DNA damage response involving the formation of nuclear foci containing phosphorylated histone H2AX and activated ATM in each cell type. In mitotic neural cells DN-TRF2 induced activation of both p53 and p21 and senescence (as indicated by an up-regulation of beta-galactosidase). In contrast, in neurons DN-TRF2 increased p21, but neither p53 nor beta-galactosidase was induced. In addition, TRF2 inhibition enhanced the morphological, molecular and biophysical differentiation of hippocampal neurons. These findings demonstrate divergent molecular and physiological responses to telomere dysfunction in mitotic neural cells and neurons, indicate a role for TRF2 in regulating neuronal differentiation, and suggest a potential therapeutic application of inhibition of TRF2 function in the treatment of neural tumors.

  3. Mitochondrial dysfunction, oxidative stress, and neurodegeneration elicited by a bacterial metabolite in a C. elegans Parkinson's model.

    PubMed

    Ray, A; Martinez, B A; Berkowitz, L A; Caldwell, G A; Caldwell, K A

    2014-01-09

    Genetic and idiopathic forms of Parkinson's disease (PD) are characterized by loss of dopamine (DA) neurons and typically the formation of protein inclusions containing the alpha-synuclein (α-syn) protein. Environmental contributors to PD remain largely unresolved but toxins, such as paraquat or rotenone, represent well-studied enhancers of susceptibility. Previously, we reported that a bacterial metabolite produced by Streptomyces venezuelae caused age- and dose-dependent DA neurodegeneration in Caenorhabditis elegans and human SH-SY5Y neurons. We hypothesized that this metabolite from a common soil bacterium could enhance neurodegeneration in combination with PD susceptibility gene mutations or toxicants. Here, we report that exposure to the metabolite in C. elegans DA neurons expressing human α-syn or LRRK2 G2019S exacerbates neurodegeneration. Using the PD toxin models 6-hydroxydopamine and rotenone, we demonstrate that exposure to more than one environmental risk factor has an additive effect in eliciting DA neurodegeneration. Evidence suggests that PD-related toxicants cause mitochondrial dysfunction, thus we examined the impact of the metabolite on mitochondrial activity and oxidative stress. An ex vivo assay of C. elegans extracts revealed that this metabolite causes excessive production of reactive oxygen species. Likewise, enhanced expression of a superoxide dismutase reporter was observed in vivo. The anti-oxidant probucol fully rescued metabolite-induced DA neurodegeneration, as well. Interestingly, the stress-responsive FOXO transcription factor DAF-16 was activated following exposure to the metabolite. Through further mechanistic analysis, we discerned the mitochondrial defects associated with metabolite exposure included adenosine triphosphate impairment and upregulation of the mitochondrial unfolded protein response. Metabolite-induced toxicity in DA neurons was rescued by complex I activators. RNA interference (RNAi) knockdown of mitochondrial

  4. Cell proliferation, viability, and in vitro differentiation of equine mesenchymal stem cells seeded on bacterial cellulose hydrogel scaffolds.

    PubMed

    Favi, Pelagie M; Benson, Roberto S; Neilsen, Nancy R; Hammonds, Ryan L; Bates, Cassandra C; Stephens, Christopher P; Dhar, Madhu S

    2013-05-01

    The culture of multipotent mesenchymal stem cells on natural biopolymers holds great promise for treatments of connective tissue disorders such as osteoarthritis. The safety and performance of such therapies relies on the systematic in vitro evaluation of the developed stem cell-biomaterial constructs prior to in vivo implantation. This study evaluates bacterial cellulose (BC), a biocompatible natural polymer, as a scaffold for equine-derived bone marrow mesenchymal stem cells (EqMSCs) for application in bone and cartilage tissue engineering. An equine model was chosen due to similarities in size, load and types of joint injuries suffered by horses and humans. Lyophilized and critical point dried BC hydrogel scaffolds were characterized using scanning electron microscopy (SEM) to confirm nanostructure morphology which demonstrated that critical point drying induces fibre bundling unlike lyophilisation. EqMSCs positively expressed the undifferentiated pluripotent mesenchymal stem cell surface markers CD44 and CD90. The BC scaffolds were shown to be cytocompatible, supporting cellular adhesion and proliferation, and allowed for osteogenic and chondrogenic differentiation of EqMSCs. The cells seeded on the BC hydrogel were shown to be viable and metabolically active. These findings demonstrate that the combination of a BC hydrogel and EqMSCs are promising constructs for musculoskeletal tissue engineering applications.

  5. Fragmented Lactic Acid Bacterial Cells Activate Peroxisome Proliferator-Activated Receptors and Ameliorate Dyslipidemia in Obese Mice.

    PubMed

    Nakamura, Futoshi; Ishida, Yu; Sawada, Daisuke; Ashida, Nobuhisa; Sugawara, Tomonori; Sakai, Manami; Goto, Tsuyoshi; Kawada, Teruo; Fujiwara, Shigeru

    2016-03-30

    Recent studies suggest that peroxisome proliferator-activated receptor (PPAR) activation ameliorates metabolic disorders, including dyslipidemia. To identify an effective PPAR agonist, we screened the in vitro PPARα/γ activation ability of organic solvent extracts from food-oriented bacterial strains belonging to 5 genera and 32 species, including lactic acid bacteria, and of these, Lactobacillus amylovorus CP1563 demonstrated the highest PPARα/γ agonist activity. We also found that physical fragmentation of the strain could substitute organic solvent extraction for the expression of CP1563 activity in vitro. For functional food manufacturing, we selected the fragmented CP1563 and conducted subsequent animal experiments. In an obese mouse model, we found that treatment with fragmented CP1563 for 12 weeks decreased the levels of low-density lipoprotein (LDL)-cholesterol and triglyceride in plasma, significantly decreased the atherosclerosis index, and increased the plasma high-density lipoprotein (HDL)-cholesterol level. Thus, we conclude that fragmented CP1563 may be a candidate for the prevention and treatment of dyslipidemia.

  6. Granulocyte Colony-Stimulating Factor Ameliorates Skeletal Muscle Dysfunction in Amyotrophic Lateral Sclerosis Mice and Improves Proliferation of SOD1-G93A Myoblasts in vitro.

    PubMed

    Rando, Amaya; Gasco, Samanta; de la Torre, Miriam; García-Redondo, Alberto; Zaragoza, Pilar; Toivonen, Janne M; Osta, Rosario

    2017-01-01

    Amyotrophic lateral sclerosis (ALS) causes loss of upper and lower motor neurons as well as skeletal muscle (SKM) dysfunction and atrophy. SKM is one of the tissues involved in the development of ALS pathology, and studies in a SOD1-G93A mouse model of ALS have demonstrated alterations in SKM degeneration/regeneration marker expression in vivo and defective mutant myoblast proliferation in vitro. Granulocyte colony-stimulating factor (G-CSF) has been shown to alleviate SOD1-G93A pathology. However, it is unknown whether G-CSF may have a direct effect on SKM or derived myoblasts. To investigate effects of G-CSF and its analog pegfilgrastim (PEGF) on SOD1-G93A- associated SKM markers in vivo and those of G-CSF on myoblast proliferation in vitro. The effect of PEGF treatment on hematopoietic stem cell mobilization, survival, and motor function was determined. RNA expression of SKM markers associated with mutant SOD1 expression was quantified in response to PEGF treatment in vivo, and the effect of G-CSF on the proliferation of myoblasts derived from mutant and control muscles was determined in vitro. Positive effects of PEGF on hematopoietic stem cell mobilization, survival, and functional assays in SOD1-G93A animals were confirmed. In vivo PEGF treatment augmented the expression of its receptor Csf3r and alleviated typical markers for mutant SOD1 muscle. Additionally, G-CSF was found to directly increase the proliferation of SOD1-G93A, but not wild-type primary myoblasts in vitro. Our results support the beneficial role of the G-CSF analog PEGF in a SOD1-G93A model of ALS. Thus, G-CSF and its analogs may be directly beneficial in diseases where the SKM function is compromised. © 2016 S. Karger AG, Basel.

  7. Vitamin K4 inhibits the proliferation and induces apoptosis of U2OS osteosarcoma cells via mitochondrial dysfunction.

    PubMed

    Di, Weihua; Khan, Muhammad; Gao, Yong; Cui, Jing; Wang, Deqiang; Qu, Mingfen; Feng, Liangtao; Maryam, Amara; Gao, Hongwen

    2017-01-01

    Vitamin K (VK) is a group of fat‑soluble vitamins, which serve important roles in blood coagulation and bone metabolism. A recent study reported that several VK subtypes possess antitumor properties, however the antitumor effects of VK in osteosarcoma are unknown. The present study aimed to identify the antitumor effects of VK in osteosarcoma and the possible underlying mechanism of action. The effect of VK4 on cell viability was determined using a 3‑(4,5‑dimethylthiazol‑2‑yl)‑2,5‑diphenyltetrazolium bromide (MTT) assay. Cellular and nuclear morphological changes were observed by phase contrast microscopy. Cell cycle analysis, apoptotic rate, mitochondrial membrane potential and levels of reactive oxygen species (ROS) were detected by flow cytometry. In vitro cancer cell migration activities were evaluated using a Wound healing assay and Transwell microplates. The results demonstrated that VK4 arrested the cells in S phase and induced apoptosis. Additional mechanistic studies indicated that the induction of apoptosis by VK4 was associated with the increased production of reactive oxygen species, dissipation of the mitochondrial membrane potential, decreased Bcl‑2 family protein expression levels and activation of caspase‑3. In conclusion, the results suggest that the sensitivity of U2OS osteosarcoma cells to VK4 may be as a result of mitochondrial dysfunction. As it is readily available for human consumption, VK4 may therefore present a novel therapeutic candidate for the treatment of patients with osteosarcoma.

  8. Early administration of probiotics alters bacterial colonization and limits diet-induced gut dysfunction and severity of necrotizing enterocolitis in preterm pigs.

    PubMed

    Siggers, Richard H; Siggers, Jayda; Boye, Mette; Thymann, Thomas; Mølbak, Lars; Leser, Thomas; Jensen, Bent B; Sangild, Per T

    2008-08-01

    Following preterm birth, bacterial colonization and enteral formula feeding predispose neonates to gut dysfunction and necrotizing enterocolitis (NEC), a serious gastrointestinal inflammatory disease. We hypothesized that administration of probiotics would beneficially influence early bacterial colonization, thereby reducing the susceptibility to formula-induced gut atrophy, dysfunction, and NEC. Caesarean-delivered preterm pigs were provided total parenteral nutrition (1.5 d) followed by enteral feeding (2 d) with porcine colostrum (COLOS; n = 5), formula (FORM; n = 9), or formula with probiotics (FORM-P; Bifidobacterium animalis and Lactobacillus: L. acidophilus, L. casei, L. pentosus, L. plantarum; n = 13). Clinical NEC scores were reduced (P < 0.05) in FORM-P (2.0 +/- 0.2) and COLOS groups (1.7 +/- 0.5) compared with FORM pigs (3.4 +/- 0.6). Lower NEC scores were associated with elevated intestinal weight, mucosa proportion, villus height, RNA integrity, and brush border aminopeptidase A and N activities, and lower gastric organic acid concentration in the FORM-P and COLOS groups (P < 0.05). Diversity of the mucosa-associated bacteria in the distal small intestine was similar among formula-fed pigs, yet the abundance of specific bacterial groups differed between FORM-P and FORM pigs. FORM-P pigs had lower colonization density of a potential pathogen, Clostridium perfringens, and had commensal Lactobacillus bacteria more closely associated with enterocytes along the villus-crypt axis relative to FORM pigs. These results suggest that probiotic administration immediately after birth promotes the colonization of a beneficial commensal microbiota capable of limiting the formula-induced mucosal atrophy, dysfunction, and pathogen load in preterm neonates, thereby reducing the incidence and severity of NEC.

  9. Antibiotic drug levofloxacin inhibits proliferation and induces apoptosis of lung cancer cells through inducing mitochondrial dysfunction and oxidative damage.

    PubMed

    Song, Meijun; Wu, Hongcheng; Wu, Shibo; Ge, Ting; Wang, Guoan; Zhou, Yingyan; Sheng, Shimo; Jiang, Jingbo

    2016-12-01

    Lung cancer is the leading cause of cancer death worldwide and its clinical management remains challenge. Here, we repurposed antibiotic levofloxacin for lung cancer treatment. We show that levofloxacin is effectively against a panel of lung cancer cell lines via inhibiting proliferation and inducing apoptosis, regardless of cellular origin and genetic pattern, in in vitro cell culture system and in vivo xenograft lung tumor model. Mechanistically, levofloxacin inhibits activities of mitochondrial electron transport chain complex I and III, leading to inhibition of mitochondrial respiration and reduction of ATP production. In addition, levofloxacin significantly increases levels of ROS, mitochondrial superoxide and hydrogen peroxide in vitro and oxidative stress markers (HEL and 4-HNE) in vivo. Antioxidants, such as NAC and vitamin C, prevent the inhibitory effects of levofloxacin, confirming the induction of oxidative damage as the mechanism of its action in lung cancer cells. Our work demonstrates that levofloxacin is a useful addition to the treatment of lung cancer. Our work also suggests that targeting mitochondria may be an alternative therapeutic strategy for lung cancer treatment.

  10. Antagonist of peroxisome proliferator-activated receptor {gamma} induces cerebellar amyloid-{beta} levels and motor dysfunction in APP/PS1 transgenic mice

    SciTech Connect

    Du, Jing; Sun, Bing; Chen, Kui; Fan, Li; Wang, Zhao

    2009-07-03

    Recent evidences show that peroxisome proliferator-activated receptor {gamma} (PPAR{gamma}) is involved in the modulation of the amyloid-{beta} (A{beta}) cascade causing Alzheimer's disease (AD) and treatment with PPAR{gamma} agonists protects against AD pathology. However, the function of PPAR{gamma} steady-state activity in A{beta} cascade and AD pathology remains unclear. In this study, an antagonist of PPAR{gamma}, GW9662, was injected into the fourth ventricle of APP/PS1 transgenic mice to inhibit PPAR{gamma} activity in cerebellum. The results show that inhibition of PPAR{gamma} significantly induced A{beta} levels in cerebellum and caused cerebellar motor dysfunction in APP/PS1 transgenic mice. Moreover, GW9662 treatment markedly decreased the cerebellar levels of insulin-degrading enzyme (IDE), which is responsible for the cellular degradation of A{beta}. Since cerebellum is spared from significant A{beta} accumulation and neurotoxicity in AD patients and animal models, these findings suggest a crucial role of PPAR{gamma} steady-state activity in protection of cerebellum against AD pathology.

  11. Activation of peroxisome proliferator-activated receptor-γ coactivator 1α ameliorates mitochondrial dysfunction and protects podocytes from aldosterone-induced injury.

    PubMed

    Yuan, Yanggang; Huang, Songming; Wang, Wenyan; Wang, Yingying; Zhang, Ping; Zhu, Chunhua; Ding, Guixia; Liu, Bicheng; Yang, Tianxin; Zhang, Aihua

    2012-10-01

    Glomerular podocytes are highly specialized epithelial cells whose injury in glomerular diseases causes proteinuria. Since mitochondrial dysfunction is an early event in podocyte injury, we tested whether a major regulator of oxidative metabolism and mitochondrial function, the transcriptional coactivator peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α), affects podocyte damage. Aldosterone-induced injury decreased PGC-1α expression, and induced mitochondrial and podocyte damage in dose- and time-dependent manners. The suppression of endogenous PGC-1α by RNAi caused podocyte mitochondrial damage and apoptosis while its increase by infection with an adenoviral vector prevented aldosterone-induced mitochondrial malfunction and inhibited injury. Overexpression of the silent mating type information regulation 2 homolog 1, a gene upstream of PGC-1α, prevented aldosterone-induced mitochondrial damage and podocyte injury by upregulating PGC-1α at both the transcriptional and post-translational levels. Resveratrol, a SIRT1 activator, attenuated aldosterone-induced mitochondrial malfunction and podocyte injury in vitro and in aldosterone-infused mice in vivo. Hence, endogenous PGC-1α may be important for maintenance of mitochondrial function in podocytes under normal conditions. Activators of SIRT1, such as resveratol, may be therapeutically useful in glomerular diseases to promote and maintain PGC-1α expression and, consequently, podocyte integrity.

  12. Whole grape intake impacts cardiac peroxisome proliferator-activated receptor and nuclear factor kappaB activity and cytokine expression in rats with diastolic dysfunction.

    PubMed

    Seymour, E Mitchell; Bennink, Maurice R; Watts, Stephanie W; Bolling, Steven F

    2010-05-01

    Prolonged hypertension is the leading cause of heart failure. Failing hearts show reduced peroxisome proliferator-activating receptor (PPAR) activity and enhanced nuclear factor kappaB (NF-kappaB) activity, which together modify cardiac inflammation and fibrosis. In vitro studies suggest that phytochemicals alter PPAR and NF-kappaB activity, but the capabilities of a phytochemical-rich diet are less understood. Grapes contain an array of commonly consumed dietary phytochemicals. In Dahl salt-sensitive hypertensive rats, we showed previously that dietary provision of whole table grape powder (3% weight:weight) for 18 weeks reduced blood pressure, cardiac hypertrophy, and diastolic dysfunction. The hypothesis tested here is that, in this model, phytochemical provision from whole grape powder impacts cardiac PPAR and NF-kappaB activity and their related gene transcripts. Grape-fed rats had enhanced PPAR-alpha and PPAR-gamma DNA binding activity but reduced NF-kappaB DNA binding activity. RT-PCR revealed that grape-fed rats showed upregulated mRNA for PPAR-alpha, PPAR-gamma coactivator-1alpha, PPAR-gamma, and the cytosolic NF-kappaB inhibitor, inhibitor-kappaBalpha. By contrast, grape-fed rats showed downregulated mRNA for tumor necrosis factor-alpha and transforming growth factor-beta1. Finally, grape-fed rats showed significantly reduced cardiac tumor necrosis factor-alpha and transforming growth factor-beta protein expression, increased inhibitor-kappaBalpha expression, and reduced cardiac fibrosis. In the Dahl salt-sensitive rat, chronic intake of grapes altered cardiac transcripts related to PPAR and NF-kappaB that may be significant to the observed diet-associated cardioprotection.

  13. Antigen-specific bacterial vaccine combined with anti-PD-L1 rescues dysfunctional endogenous T cells to reject long-established cancer.

    PubMed

    Binder, David C; Engels, Boris; Arina, Ainhoa; Yu, Ping; Slauch, James M; Fu, Yang-Xin; Karrison, Theodore; Burnette, Byron; Idel, Christian; Zhao, Ming; Hoffman, Robert M; Munn, David H; Rowley, Donald A; Schreiber, Hans

    2013-08-01

    Immunogenic tumors grow progressively even when heavily infiltrated by CD8(+) T cells. We investigated how to rescue CD8(+) T cell function in long-established immunogenic melanomas that contained a high percentage of endogenous PD-1(+) tumor-specific CD8(+) T cells that were dysfunctional. Treatment with αPD-L1 and αCTLA-4 blocking antibodies did not prevent tumors from progressing rapidly. We then tested exogenous tumor-specific antigen delivery into tumors using Salmonella Typhimurium A1-R to increase antigen levels and generate a proinflammatory tumor microenvironment. Antigen-producing A1-R rescued the endogenous tumor-specific CD8(+) T cell response: proliferation was induced in the lymphoid organs and effector function was recovered in the tumor. Treatment with antigen-producing A1-R led to improved mouse survival and resulted in 32% rejection of long-established immunogenic melanomas. Following treatment with antigen-producing A1-R, the majority of tumor-specific CD8(+) T cells still expressed a high level of PD-1 in the tumor. Combining antigen-producing A1-R with αPD-L1 blocking antibody enhanced the expansion of tumor-specific CD8(+) T cells and resulted in 80% tumor rejection. Collectively, these data demonstrate a powerful new therapeutic approach to rescue dysfunctional endogenous tumor-specific CD8(+) T cells and eradicate advanced immunogenic tumors.

  14. The DinJ/RelE toxin-antitoxin system suppresses bacterial proliferation and virulence of Xylella fastidiosa in grapevine

    USDA-ARS?s Scientific Manuscript database

    Xylella fastidiosa, the causal agent of Pierce’s disease of grapes, is a slow-growing, xylem-limited, bacterial pathogen. Disease progression is characterized by systemic spread of the bacterium through xylem vessel networks, causing leaf scorching symptoms, senescence, and vine decline. It appears ...

  15. Protective Capacity of Resveratrol, a Natural Polyphenolic Compound, against Deoxynivalenol-Induced Intestinal Barrier Dysfunction and Bacterial Translocation.

    PubMed

    Ling, Ka-Ho; Wan, Murphy Lam Yim; El-Nezami, Hani; Wang, Mingfu

    2016-05-16

    Contamination of food/feedstuffs by mycotoxins is a serious problem worldwide, causing severe economic losses and serious health problems in animals/humans. Deoxynivalenol (DON) is a major mycotoxin contaminant and is known to impair intestinal barrier function. Grapes and red wine are rich in polyphenols, such as resveratrol (RES), which has striking antioxidant and anti-inflammatory activities. RES is a food-derived component; therefore, it may be simultaneously present with DON in the gastrointestinal tract. The aim of this study was to explore in vitro protective effects of RES against DON-induced intestinal damage. The results showed that RES could protect DON-induced bacteria translocation because of enhanced of intestinal barrier function by restoring the DON-induced decrease in transepithelial electrical resistance and increase in paracellular permeability. Further mechanistic studies demonstrated that RES protects against DON-induced barrier dysfunction by promoting the assembly of claudin-4 in the tight junction complex. This is probably mediated through modulation of IL-6 and IL-8 secretion via mitogen-activated protein kinase-dependent pathways. Our results imply that RES can protect against DON-induced intestinal damage and that RES may be used as a novel dietary intervention strategy to reduce DON toxicity in animals/humans.

  16. Peroxisome Proliferator-Activated Receptor γ Regulates the V-Ets Avian Erythroblastosis Virus E26 Oncogene Homolog 1/microRNA-27a Axis to Reduce Endothelin-1 and Endothelial Dysfunction in the Sickle Cell Mouse Lung.

    PubMed

    Kang, Bum-Yong; Park, Kathy; Kleinhenz, Jennifer M; Murphy, Tamara C; Sutliff, Roy L; Archer, David; Hart, C Michael

    2017-01-01

    Pulmonary hypertension (PH), a serious complication of sickle cell disease (SCD), causes significant morbidity and mortality. Although a recent study determined that hemin release during hemolysis triggers endothelial dysfunction in SCD, the pathogenesis of SCD-PH remains incompletely defined. This study examines peroxisome proliferator-activated receptor γ (PPARγ) regulation in SCD-PH and endothelial dysfunction. PH and right ventricular hypertrophy were studied in Townes humanized sickle cell (SS) and littermate control (AA) mice. In parallel studies, SS or AA mice were gavaged with the PPARγ agonist, rosiglitazone (RSG), 10 mg/kg/day, or vehicle for 10 days. In vitro, human pulmonary artery endothelial cells (HPAECs) were treated with vehicle or hemin for 72 hours, and selected HPAECs were treated with RSG. SS mice developed PH and right ventricular hypertrophy associated with reduced lung levels of PPARγ and increased levels of microRNA-27a (miR-27a), v-ets avian erythroblastosis virus E26 oncogene homolog 1 (ETS1), endothelin-1 (ET-1), and markers of endothelial dysfunction (platelet/endothelial cell adhesion molecule 1 and E selectin). HPAECs treated with hemin had increased ETS1, miR-27a, ET-1, and endothelial dysfunction and decreased PPARγ levels. These derangements were attenuated by ETS1 knockdown, inhibition of miR-27a, or PPARγ overexpression. In SS mouse lung or in hemin-treated HPAECs, activation of PPARγ with RSG attenuated reductions in PPARγ and increases in miR-27a, ET-1, and markers of endothelial dysfunction. In SCD-PH pathogenesis, ETS1 stimulates increases in miR-27a levels that reduce PPARγ and increase ET-1 and endothelial dysfunction. PPARγ activation attenuated SCD-associated signaling derangements, suggesting a novel therapeutic approach to attenuate SCD-PH pathogenesis.

  17. The pepper MLO gene, CaMLO2, is involved in the susceptibility cell-death response and bacterial and oomycete proliferation.

    PubMed

    Kim, Dae Sung; Hwang, Byung Kook

    2012-12-01

    Loss-of-function alleles of the mildew resistance locus O (MLO) gene provide broad-spectrum powdery mildew disease resistance. Here, we identified a pepper (Capsicum annuum) MLO gene (CaMLO2) that is transcriptionally induced by Xanthomonas campestris pv. vesicatoria (Xcv) infection. Topology and subcellular localization analyses reveal that CaMLO2 is a plasma membrane-anchored and amphiphilic Ca²⁺-dependent calmodulin-binding protein. CaMLO2 expression is up-regulated by Xcv and salicylic acid, as well as abiotic stresses. Silencing of CaMLO2 in pepper plants confers enhanced resistance against virulent Xcv, but not against avirulent Xcv. This resistance is accompanied by a compromised susceptibility cell-death response and reduced bacterial growth, as well as an accelerated reactive oxygen species burst. Virulent Xcv infection drastically induces expression of the salicylic acid-dependent defense marker gene CaPR1 in CaMLO2-silenced leaves. CaMLO2 over-expression in Arabidopsis enhances susceptibility to Pseudomonas syringae pv. tomato and Hyaloperonospora arabidopsidis. Leaves of plants over-expressing CaMLO2 exhibit a susceptibility cell-death response and high bacterial growth during virulent Pst DC3000 infection. These are accompanied by enhanced electrolyte leakage but compromised induction of some defense response genes and the reactive oxygen species. Together, our results suggest that CaMLO2 is involved in the susceptibility cell-death response and bacterial and oomycete proliferation in pepper and Arabidopsis. © 2012 The Authors. The Plant Journal © 2012 Blackwell Publishing Ltd.

  18. Vesicular Stomatitis Virus-Vectored Multi-Antigen Tuberculosis Vaccine Limits Bacterial Proliferation in Mice following a Single Intranasal Dose

    PubMed Central

    Zhang, Ming; Dong, Chunsheng; Xiong, Sidong

    2017-01-01

    Tuberculosis (TB) remains a serious health problem worldwide, and an urgent need exists to improve or replace the available vaccine, Mycobacterium bovis bacillus Calmette-Guérin (BCG). Most vaccination protocols adapt two or three doses to induce long-term lasting immunity. Our previous study showed that the naked DNA encoding the triple-antigen fusion TFP846 (Rv3615c-Mtb10.4-Rv2660c) induced robust T cellular immune responses accompanying four inoculations against mycobacteria infection. However, a number of compliance issues exist in some areas lacking the appropriate medical infrastructure with multiple administrations. In this study, a novel vesicular stomatitis virus expressing TFP846 (VSV-846) was developed and the immune responses elicited by VSV-846 were evaluated. We observed that intranasal delivery of VSV-846 induced a potent antigen-specific T cell response following a single dose and VSV-846 efficiently controlled bacterial growth to levels ~10-fold lower than that observed in the mock group 6 weeks post-infection in BCG-infected mice. Importantly, mice immunized with VSV-846 provided long-term protection against mycobacteria infection compared with those receiving p846 or BCG immunization. Increased memory T cells were also observed in the spleens of VSV-846-vaccinated mice, which could be a potential mechanism associated with long-term protective immune response. These findings supported the use of VSV as an antigen delivery vector with the potential for TB vaccine development. PMID:28224119

  19. Metabolites related to gut bacterial metabolism, peroxisome proliferator-activated receptor-alpha activation, and insulin sensitivity are associated with physical function in functionally-limited older adults

    PubMed Central

    Lustgarten, Michael S; Price, Lori L; Chalé, Angela; Fielding, Roger A

    2014-01-01

    Identification of mechanisms underlying physical function will be important for addressing the growing challenge that health care will face with physical disablement in the expanding aging population. Therefore, the goals of the current study were to use metabolic profiling to provide insight into biologic mechanisms that may underlie physical function by examining the association between baseline and the 6-month change in serum mass spectrometry-obtained amino acids, fatty acids, and acylcarnitines with baseline and the 6-month change in muscle strength (leg press one repetition maximum divided by total lean mass, LP/Lean), lower extremity function [short physical performance battery (SPPB)], and mobility (400 m gait speed, 400-m), in response to 6 months of a combined resistance exercise and nutritional supplementation (whey protein or placebo) intervention in functionally-limited older adults (SPPB ≤ 10; 70–85 years, N = 73). Metabolites related to gut bacterial metabolism (cinnamoylglycine, phenol sulfate, p-cresol sulfate, 3-indoxyl sulfate, serotonin, N-methylproline, hydrocinnamate, dimethylglycine, trans-urocanate, valerate) that are altered in response to peroxisome proliferator-activated receptor-alpha (PPAR-α) activation (α-hydroxyisocaproate, α-hydroxyisovalerate, 2-hydroxy-3-methylvalerate, indolelactate, serotonin, 2-hydroxypalmitate, glutarylcarnitine, isobutyrylcarnitine, cinnamoylglycine) and that are related to insulin sensitivity (monounsaturated fatty acids: 5-dodecenoate, myristoleate, palmitoleate; γ-glutamylamino acids: γ-glutamylglutamine, γ-glutamylalanine, γ-glutamylmethionine, γ-glutamyltyrosine; branched-chain amino acids: leucine, isoleucine, valine) were associated with function at baseline, with the 6-month change in function or were identified in backward elimination regression predictive models. Collectively, these data suggest that gut microbial metabolism, PPAR-α activation, and insulin sensitivity may be involved in

  20. Myocardial fibrosis and diastolic dysfunction in deoxycorticosterone acetate-salt hypertensive rats is ameliorated by the peroxisome proliferator-activated receptor-alpha activator fenofibrate, partly by suppressing inflammatory responses associated with the nuclear factor-kappa-B pathway.

    PubMed

    Ogata, Takehiro; Miyauchi, Takashi; Sakai, Satoshi; Takanashi, Masakatsu; Irukayama-Tomobe, Yoko; Yamaguchi, Iwao

    2004-04-21

    We sought to clarify that a peroxisome proliferator-activated receptor-alpha (PPAR-alpha) activator inhibits myocardial fibrosis and its resultant diastolic dysfunction in hypertensive heart disease, as well as to investigate whether inflammatory mediators through the nuclear factor (NF)-kappa-B pathway are involved in the effects. Patients with hypertensive heart disease often have diastolic heart failure without systolic dysfunction. Meanwhile, it has been well established in atherosclerosis that PPAR-alpha activation negatively regulates early inflammation. In hypertensive hearts, however, it is still unclear whether PPAR-alpha activation inhibits inflammation and fibrosis. Twenty-one rats were randomly separated into the following three groups: deoxycorticosterone acetate (DOCA)-salt hypertensive rats treated with a PPAR-alpha activator, fenofibrate (80 mg/kg/day for 5 weeks); DOCA-salt rats treated with vehicle only; and uni-nephrectomized rats as normotensive controls. Fenofibrate significantly inhibited the elevation of left ventricular end-diastolic pressure and the reduction of the magnitude of the negative maximum rate of left ventricular pressure rise and decline, corrected by left ventricular pressure (-dP/dt(max)/P), which are indicators of diastolic dysfunction. Next, fenofibrate prevented myocardial fibrosis and reduced the hydroxyproline content and procollagen I and III messenger ribonucleic acid expression. Finally, inflammatory gene expression associated with NF-kappa-B (interleukin-6, cyclooxygenase-2, vascular cell adhesion molecule-1, and monocyte chemoattractant protein-1), which is upregulated in DOCA-salt rats, was significantly suppressed by fenofibrate. Activation of NF-kappa-B and expression of I-kappa-B-alpha in DOCA-salt rats were normalized by fenofibrate. A PPAR-alpha activator reduced myocardial fibrosis and prevented the development of diastolic dysfunction in DOCA-salt rats. The effects of a PPAR-alpha activator may be mediated

  1. Dysfunctional BLK in common variable immunodeficiency perturbs B-cell proliferation and ability to elicit antigen-specific CD4+ T-cell help.

    PubMed

    Compeer, Ewoud B; Janssen, Willemijn; van Royen-Kerkhof, Annet; van Gijn, Marielle; van Montfrans, Joris M; Boes, Marianne

    2015-05-10

    Common Variable Immunodeficiency (CVID) is the most prevalent primary antibody deficiency, and characterized by defective generation of high-affinity antibodies. Patients have therefore increased risk to recurrent infections of the respiratory and intestinal tract. Development of high-affinity antigen-specific antibodies involves two key actions of B-cell receptors (BCR): transmembrane signaling through BCR-complexes to induce B-cell differentiation and proliferation, and BCR-mediated antigen internalization for class-II MHC-mediated presentation to acquire antigen-specific CD4(+) T-cell help.We identified a variant (L3P) in the B-lymphoid tyrosine kinase (BLK) gene of 2 related CVID-patients, which was absent in healthy relatives. BLK belongs to the Src-kinases family and involved in BCR-signaling. Here, we sought to clarify BLK function in healthy human B-cells and its association to CVID.BLK expression was comparable in patient and healthy B-cells. Functional analysis of L3P-BLK showed reduced BCR crosslinking-induced Syk phosphorylation and proliferation, in both primary B-cells and B-LCLs. B-cells expressing L3P-BLK showed accelerated destruction of BCR-internalized antigen and reduced ability to elicit CD40L-expression on antigen-specific CD4(+) T-cells.In conclusion, we found a novel BLK gene variant in CVID-patients that causes suppressed B-cell proliferation and reduced ability of B-cells to elicit antigen-specific CD4(+) T-cell responses. Both these mechanisms may contribute to hypogammaglobulinemia in CVID-patients.

  2. A novel 2,3-diphenyl-4H-pyrido[1,2-a]pyrimidin-4-one derivative inhibits endothelial cell dysfunction and smooth muscle cell proliferation/activation.

    PubMed

    Del Turco, Serena; Sartini, Stefania; Sentieri, Cassandra; Saponaro, Chiara; Navarra, Teresa; Dario, Bianca; Da Settimo, Federico; La Motta, Concettina; Basta, Giuseppina

    2014-01-24

    Hyper-proliferation and migration of vascular smooth muscle cells and endothelial cell dysfunction are central events in the development of neo-intimal lesions. Pursuing our interest in the synthesis of bioisosters of flavonoids, we studied in depth a novel synthetic 2,3-diphenyl-4H-pyrido[1,2-a]pyrimidin-4-one derivative, examining its effects in vitro on induced-cell proliferation and activation in human aortic smooth muscle cells (HAoSMCs) and in human umbilical vein endothelial cells (HUVECs). Compared with two well known flavonoids, apigenin and quercetin, the novel compound, 2-(3,4-dimethoxyphenyl)-3-phenyl-4H-pyrido[1,2-a]pyrimidin-4-one, 3, was not toxic for HUVECs, even at high concentrations and for long incubation times, while the two flavonoids were not tolerated, even at concentrations as low as 10 μmol/L. Compound 3 inhibited selectively, and in a concentration-dependent manner, the proliferation of HAoSMCs but not that of HUVECs. In HUVECs, it inhibited the cytokine-induced vascular cell adhesion molecule-1 expression, but not the cyclooxygenase-2 (COX-2) expression. Instead, in HAoSMC, it inhibited the induction of COX-2 expression and the relative release of prostaglandin E2. In addition, it inhibited the transcription of the matrix metalloproteinase-9 and its activity. Thanks to its multiple and tissue-specific function, 2-(3,4-dimethoxyphenyl)-3-phenyl-4H-pyrido[1,2-a]pyrimidin-4-one might replace or assist the action of current drugs eluted by coronary stents, in order to promote a functional repair of damaged wall. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  3. Immune Dysfunction in Cirrhosis

    PubMed Central

    Noor, Mohd Talha; Manoria, Piyush

    2017-01-01

    Abstract Cirrhosis due to any etiology disrupts the homeostatic role of liver in the body. Cirrhosis-associated immune dysfunction leads to alterations in both innate and acquired immunity, due to defects in the local immunity of liver as well as in systemic immunity. Cirrhosis-associated immune dysfunction is a dynamic phenomenon, comprised of both increased systemic inflammation and immunodeficiency, and is responsible for 30% mortality. It also plays an important role in acute as well as chronic decompensation. Immune paralysis can accompany it, which is characterized by increase in anti-inflammatory cytokines and suppression of proinflammatory cytokines. There is also presence of increased gut permeability, reduced gut motility and altered gut flora, all of which leads to increased bacterial translocation. This increased bacterial translocation and consequent endotoxemia leads to increased blood stream bacterial infections that cause systemic inflammatory response syndrome, sepsis, multiorgan failure and death. The gut microbiota of cirrhotic patients has more pathogenic microbes than that of non-cirrhotic individuals, and this disturbs the homeostasis and favors gut translocation. Prompt diagnosis and treatment of such infections are necessary for better survival. We have reviewed the various mechanisms of immune dysfunction and its consequences in cirrhosis. Recognizing the exact pathophysiology of immune dysfunction will help treating clinicians in avoiding its complications in their patients and can lead to newer therapeutic interventions and reducing the morbidity and mortality rates. PMID:28507927

  4. Orgasmic dysfunction

    MedlinePlus

    Inhibited sexual excitement; Sex - orgasmic dysfunction; Anorgasmia; Sexual dysfunction - orgasmic; Sexual problem - orgasmic ... of knowledge about sexual function Negative feelings about sex (often learned in childhood or teen years) Shyness ...

  5. Erectile Dysfunction

    MedlinePlus

    ... PCF? Featured Blue Jacket Fashion Show Contact Us Erectile Dysfunction Regardless of whether the nerves were spared during ... time returning to pre-treatment function. Management of Erectile Dysfunction When a man is sexually aroused, the erectile ...

  6. Immune dysfunction in cirrhosis

    PubMed Central

    Sipeki, Nora; Antal-Szalmas, Peter; Lakatos, Peter L; Papp, Maria

    2014-01-01

    Innate and adaptive immune dysfunction, also referred to as cirrhosis-associated immune dysfunction syndrome, is a major component of cirrhosis, and plays a pivotal role in the pathogenesis of both the acute and chronic worsening of liver function. During the evolution of the disease, acute decompensation events associated with organ failure(s), so-called acute-on chronic liver failure, and chronic decompensation with progression of liver fibrosis and also development of disease specific complications, comprise distinct clinical entities with different immunopathology mechanisms. Enhanced bacterial translocation associated with systemic endotoxemia and increased occurrence of systemic bacterial infections have substantial impacts on both clinical situations. Acute and chronic exposure to bacteria and/or their products, however, can result in variable clinical consequences. The immune status of patients is not constant during the illness; consequently, alterations of the balance between pro- and anti-inflammatory processes result in very different dynamic courses. In this review we give a detailed overview of acquired immune dysfunction and its consequences for cirrhosis. We demonstrate the substantial influence of inherited innate immune dysfunction on acute and chronic inflammatory processes in cirrhosis caused by the pre-existing acquired immune dysfunction with limited compensatory mechanisms. Moreover, we highlight the current facts and future perspectives of how the assessment of immune dysfunction can assist clinicians in everyday practical decision-making when establishing treatment and care strategies for the patients with end-stage liver disease. Early and efficient recognition of inappropriate performance of the immune system is essential for overcoming complications, delaying progression and reducing mortality. PMID:24627592

  7. Erectile dysfunction.

    PubMed

    Shamloul, Rany; Ghanem, Hussein

    2013-01-12

    Erectile dysfunction is a common clinical entity that affects mainly men older than 40 years. In addition to the classical causes of erectile dysfunction, such as diabetes mellitus and hypertension, several common lifestyle factors, such as obesity, limited or an absence of physical exercise, and lower urinary tract symptoms, have been linked to the development of erectile dysfunction. Substantial steps have been taken in the study of the association between erectile dysfunction and cardiovascular disease. Erectile dysfunction is a strong predictor for coronary artery disease, and cardiovascular assessment of a non-cardiac patient presenting with erectile dysfunction is now recommended. Substantial advances have occurred in the understanding of the pathophysiology of erectile dysfunction that ultimately led to the development of successful oral therapies, namely the phosphodiesterase type 5 inhibitors. However, oral phosphodiesterase type 5 inhibitors have limitations, and present research is thus investigating cutting-edge therapeutic strategies including gene and cell-based technologies with the aim of discovering a cure for erectile dysfunction.

  8. Erectile Dysfunction

    MedlinePlus

    ... your erectile problems, such as drugs used to treat depression or high blood pressure. Making a change to your medications may help. Seek counseling. Anxiety and stress can worsen erectile dysfunction. A psychologist or other mental health provider can ...

  9. Erectile Dysfunction

    MedlinePlus

    ... can — over time — cause chronic health conditions that lead to erectile dysfunction Being overweight, especially if you're obese Certain medical treatments, such as prostate surgery or radiation treatment for cancer Injuries, particularly if they damage ...

  10. Erectile dysfunction

    PubMed Central

    Yafi, Faysal A.; Jenkins, Lawrence; Albersen, Maarten; Corona, Giovanni; Isidori, Andrea M.; Goldfarb, Shari; Maggi, Mario; Nelson, Christian J.; Parish, Sharon; Salonia, Andrea; Tan, Ronny; Mulhall, John P.; Hellstrom, Wayne J. G.

    2016-01-01

    Erectile dysfunction is a multidimensional but common male sexual dysfunction that involves an alteration in any of the components of the erectile response, including organic, relational and psychological. Roles for nonendocrine (neurogenic, vasculogenic and iatrogenic) and endocrine pathways have been proposed. Owing to its strong association with metabolic syndrome and cardiovascular disease, cardiac assessment may be warranted in men with symptoms of erectile dysfunction. Minimally invasive interventions to relieve the symptoms of erectile dysfunction include lifestyle modifications, oral drugs, injected vasodilator agents and vacuum erection devices. Surgical therapies are reserved for the subset of patients who have contraindications to these nonsurgical interventions, those who experience adverse effects from (or are refractory to) medical therapy and those who also have penile fibrosis or penile vascular insufficiency. Erectile dysfunction can have deleterious effects on a man’s quality of life; most patients have symptoms of depression and anxiety related to sexual performance. These symptoms, in turn, affect his partner’s sexual experience and the couple’s quality of life. This Primer highlights numerous aspects of erectile dysfunction, summarizes new treatment targets and ongoing preclinical studies that evaluate new pharmacotherapies, and covers the topic of regenerative medicine, which represents the future of sexual medicine. PMID:27188339

  11. Erectile dysfunction.

    PubMed

    Wylie, Kevan

    2008-01-01

    Erectile dysfunction is a common problem affecting sexual function in men. Approximately one in 10 men over the age of 40 is affected by this condition and the incidence is age related. Erectile dysfunction is a sentinel marker for several reversible conditions including peripheral and coronary vascular disease, hypertension and diabetes mellitus. Endothelial dysfunction is a common factor between the disease states. Concurrent conditions such as depression, late-onset hypogonadism, Peyronie's disease and lower urinary tract symptoms may significantly worsen erectile function, other sexual and relationship issues and penis dysmorphophobia. A focused physical examination and baseline laboratory investigations are mandatory. Management consists of initiating modifiable lifestyle changes, psychological and psychosexual/couples interventions and pharmacological and other interventions. In combination and with treatment of concurrent comorbid states, these interventions will often bring about successful resolution of symptoms and avoid the need for surgical interventions.

  12. Gustatory dysfunction

    PubMed Central

    Maheswaran, T.; Abikshyeet, P.; Sitra, G.; Gokulanathan, S.; Vaithiyanadane, V.; Jeelani, S.

    2014-01-01

    Tastes in humans provide a vital tool for screening soluble chemicals for food evaluation, selection, and avoidance of potentially toxic substances. Taste or gustatory dysfunctions are implicated in loss of appetite, unintended weight loss, malnutrition, and reduced quality of life. Dental practitioners are often the first clinicians to be presented with complaints about taste dysfunction. This brief review provides a summary of the common causes of taste disorders, problems associated with assessing taste function in a clinical setting and management options available to the dental practitioner. PMID:25210380

  13. Memory Dysfunction

    PubMed Central

    Matthews, Brandy R.

    2015-01-01

    Purpose of Review: This article highlights the dissociable human memory systems of episodic, semantic, and procedural memory in the context of neurologic illnesses known to adversely affect specific neuroanatomic structures relevant to each memory system. Recent Findings: Advances in functional neuroimaging and refinement of neuropsychological and bedside assessment tools continue to support a model of multiple memory systems that are distinct yet complementary and to support the potential for one system to be engaged as a compensatory strategy when a counterpart system fails. Summary: Episodic memory, the ability to recall personal episodes, is the subtype of memory most often perceived as dysfunctional by patients and informants. Medial temporal lobe structures, especially the hippocampal formation and associated cortical and subcortical structures, are most often associated with episodic memory loss. Episodic memory dysfunction may present acutely, as in concussion; transiently, as in transient global amnesia (TGA); subacutely, as in thiamine deficiency; or chronically, as in Alzheimer disease. Semantic memory refers to acquired knowledge about the world. Anterior and inferior temporal lobe structures are most often associated with semantic memory loss. The semantic variant of primary progressive aphasia (svPPA) is the paradigmatic disorder resulting in predominant semantic memory dysfunction. Working memory, associated with frontal lobe function, is the active maintenance of information in the mind that can be potentially manipulated to complete goal-directed tasks. Procedural memory, the ability to learn skills that become automatic, involves the basal ganglia, cerebellum, and supplementary motor cortex. Parkinson disease and related disorders result in procedural memory deficits. Most memory concerns warrant bedside cognitive or neuropsychological evaluation and neuroimaging to assess for specific neuropathologies and guide treatment. PMID:26039844

  14. Erectile dysfunction.

    PubMed

    McMahon, C G

    2014-01-01

    In the past 30 years, advances in basic science have been instrumental in the evolution of the male sexual health treatment paradigm from a psychosexual model to a new model, which includes oral and intracavernosal injection pharmacotherapy, vacuum constriction devices and penile prostheses for the treatment of erectile dysfunction. This progress has coincided with an increased understanding of the nature of male sexual health problems, and epidemiological data that confirm that these problems are widely prevalent and the source of considerable morbidity, both for individuals and within relationships.

  15. Executive Dysfunction

    PubMed Central

    Rabinovici, Gil D.; Stephens, Melanie L.; Possin, Katherine L.

    2015-01-01

    Purpose of Review: Executive functions represent a constellation of cognitive abilities that drive goal-oriented behavior and are critical to the ability to adapt to an ever-changing world. This article provides a clinically oriented approach to classifying, localizing, diagnosing, and treating disorders of executive function, which are pervasive in clinical practice. Recent Findings: Executive functions can be split into four distinct components: working memory, inhibition, set shifting, and fluency. These components may be differentially affected in individual patients and act together to guide higher-order cognitive constructs such as planning and organization. Specific bedside and neuropsychological tests can be applied to evaluate components of executive function. While dysexecutive syndromes were first described in patients with frontal lesions, intact executive functioning relies on distributed neural networks that include not only the prefrontal cortex, but also the parietal cortex, basal ganglia, thalamus, and cerebellum. Executive dysfunction arises from injury to any of these regions, their white matter connections, or neurotransmitter systems. Dysexecutive symptoms therefore occur in most neurodegenerative diseases and in many other neurologic, psychiatric, and systemic illnesses. Management approaches are patient specific and should focus on treatment of the underlying cause in parallel with maximizing patient function and safety via occupational therapy and rehabilitation. Summary: Executive dysfunction is extremely common in patients with neurologic disorders. Diagnosis and treatment hinge on familiarity with the clinical components and neuroanatomic correlates of these complex, high-order cognitive processes. PMID:26039846

  16. Carbohydrate Metabolism Is Perturbed in Peroxisome-deficient Hepatocytes Due to Mitochondrial Dysfunction, AMP-activated Protein Kinase (AMPK) Activation, and Peroxisome Proliferator-activated Receptor γ Coactivator 1α (PGC-1α) Suppression*

    PubMed Central

    Peeters, Annelies; Fraisl, Peter; van den Berg, Sjoerd; Ver Loren van Themaat, Emiel; Van Kampen, Antoine; Rider, Mark H.; Takemori, Hiroshi; van Dijk, Ko Willems; Van Veldhoven, Paul P.; Carmeliet, Peter; Baes, Myriam

    2011-01-01

    Hepatic peroxisomes are essential for lipid conversions that include the formation of mature conjugated bile acids, the degradation of branched chain fatty acids, and the synthesis of docosahexaenoic acid. Through unresolved mechanisms, deletion of functional peroxisomes from mouse hepatocytes (L-Pex5−/− mice) causes severe structural and functional abnormalities at the inner mitochondrial membrane. We now demonstrate that the peroxisomal and mitochondrial anomalies trigger energy deficits, as shown by increased AMP/ATP and decreased NAD+/NADH ratios. This causes suppression of gluconeogenesis and glycogen synthesis and up-regulation of glycolysis. As a consequence, L-Pex5−/− mice combust more carbohydrates resulting in lower body weights despite increased food intake. The perturbation of carbohydrate metabolism does not require a long term adaptation to the absence of functional peroxisomes as similar metabolic changes were also rapidly induced by acute elimination of Pex5 via adenoviral administration of Cre. Despite its marked activation, peroxisome proliferator-activated receptor α (PPARα) was not causally involved in these metabolic perturbations, because all abnormalities still manifested when peroxisomes were eliminated in a peroxisome proliferator-activated receptor α null background. Instead, AMP-activated kinase activation was responsible for the down-regulation of glycogen synthesis and induction of glycolysis. Remarkably, PGC-1α was suppressed despite AMP-activated kinase activation, a paradigm not previously reported, and they jointly contributed to impaired gluconeogenesis. In conclusion, lack of functional peroxisomes from hepatocytes results in marked disturbances of carbohydrate homeostasis, which are consistent with adaptations to an energy deficit. Because this is primarily due to impaired mitochondrial ATP production, these L-Pex5-deficient livers can also be considered as a model for secondary mitochondrial hepatopathies. PMID

  17. Family dysfunction

    PubMed Central

    Hayaki, Chie; Anno, Kozo; Shibata, Mao; Iwaki, Rie; Kawata, Hiroshi; Sudo, Nobuyuki; Hosoi, Masako

    2016-01-01

    Abstract Previous studies have shown differences in the psychosocial factors related to chronic localized pain (CLP) and chronic widespread pain (CWP). However, no studies have done an evaluation of differences between CLP and CWP from the viewpoint of family functioning. We did a cross-sectional study in a tertiary care setting to investigate possible differences in the relation of CWP and CLP to family functioning. Patients with CLP (N = 126) or CWP (N = 75) were assessed for family functioning by the Family Assessment Device (FAD) and a comparison was done. Logistic regression analysis was used to estimate associations of family functioning subscales with pain status (CWP vs CLP), controlling for demographic variables, pain variables; pain duration, pain ratings, pain disability, and psychological factors; depression, anxiety, and catastrophizing. The odds ratios (ORs) for the presence of CWP were calculated. Compared to patients with CLP, patients with CWP showed a lower functional status for Roles and Affective Involvement. The ORs for CWP were significantly higher in lower functioning Roles (OR: 2.38, 95% CI: 1.21–4.65) and Affective Involvement (OR: 2.86, 95% CI: 1.56–5.24) after adjusting for demographic variables. The significant association of CWP to Roles and Affective Involvement remained after controlling for the pain variables and psychological factors. This study shows that the families of patients with CWP have poorer family functioning than those with CLP. Our findings suggest that early identification and interventions for the family dysfunction of chronic pain patients are important to the treatment and prevention of CWP. PMID:27930535

  18. Bacterial proteases: targets for diagnostics and therapy.

    PubMed

    Kaman, W E; Hays, J P; Endtz, H P; Bikker, F J

    2014-07-01

    Proteases are essential for the proliferation and growth of bacteria, and are also known to contribute to bacterial virulence. This makes them interesting candidates as diagnostic and therapeutic targets for infectious diseases. In this review, the authors discuss the most recent developments and potential applications for bacterial proteases in the diagnosis and treatment of bacterial infections. Current and future bacterial protease targets are described and their limitations outlined.

  19. Bacterial Vaginosis

    MedlinePlus

    ... Form Controls Cancel Submit Search the CDC Bacterial Vaginosis (BV) Note: Javascript is disabled or is not ... STD on Facebook Sexually Transmitted Diseases (STDs) Bacterial Vaginosis – CDC Fact Sheet Language: English (US) Españ ...

  20. Bacterial Sialidase

    NASA Technical Reports Server (NTRS)

    2004-01-01

    Data shows that elevated sialidase in bacterial vaginosis patients correlates to premature births in women. Bacterial sialidase also plays a significant role in the unusual colonization of Pseudomonas aeruginosa in cystic fibrosis patients. Crystals of Salmonella sialidase have been reproduced and are used for studying the inhibitor-enzyme complexes. These inhibitors may also be used to inhibit a trans-sialidase of Trypanosome cruzi, a very similar enzyme to bacterial sialidase, therefore preventing T. cruzi infection, the causitive agent of Chagas' disease. The Center for Macromolecular Crystallography suggests that inhibitors of bacterial sialidases can be used as prophylactic drugs to prevent bacterial infections in these critical cases.

  1. Bacterial Sialidase

    NASA Technical Reports Server (NTRS)

    2004-01-01

    Data shows that elevated sialidase in bacterial vaginosis patients correlates to premature births in women. Bacterial sialidase also plays a significant role in the unusual colonization of Pseudomonas aeruginosa in cystic fibrosis patients. Crystals of Salmonella sialidase have been reproduced and are used for studying the inhibitor-enzyme complexes. These inhibitors may also be used to inhibit a trans-sialidase of Trypanosome cruzi, a very similar enzyme to bacterial sialidase, therefore preventing T. cruzi infection, the causitive agent of Chagas' disease. The Center for Macromolecular Crystallography suggests that inhibitors of bacterial sialidases can be used as prophylactic drugs to prevent bacterial infections in these critical cases.

  2. Mitochondrial Dysfunction in Airway Disease.

    PubMed

    Prakash, Y S; Pabelick, Christina M; Sieck, Gary C

    2017-09-01

    There is increasing appreciation that mitochondria serve cellular functions beyond oxygen sensing and energy production. Accordingly, it has become important to explore noncanonical roles of mitochondria in normal and pathophysiological processes that influence airway structure and function in the context of diseases such as asthma and COPD. Mitochondria can sense upstream processes such as inflammation, infection, tobacco smoke, and environmental insults important in these diseases and in turn can respond to such stimuli through altered mitochondrial protein expression, structure, and resultant dysfunction. Conversely, mitochondrial dysfunction has downstream influences on cytosolic and mitochondrial calcium regulation, airway contractility, gene and protein housekeeping, responses to oxidative stress, proliferation, apoptosis, fibrosis, and certainly metabolism, which are all key aspects of airway disease pathophysiology. Indeed, mitochondrial dysfunction is thought to play a role even in normal processes such as aging and senescence and in conditions such as obesity, which impact airway diseases. Thus, understanding how mitochondrial structure and function play central roles in airway disease may be critical for the development of novel therapeutic avenues targeting dysfunctional mitochondria. In this case, it is likely that mitochondria of airway epithelium, smooth muscle, and fibroblasts play differential roles, consistent with their contributions to disease biology, underlining the challenge of targeting a ubiquitous cellular element of existential importance. This translational review summarizes the current state of understanding of mitochondrial processes that play a role in airway disease pathophysiology and identifying areas of unmet research need and opportunities for novel therapeutic strategies. Copyright © 2017 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

  3. Telomere dysfunction induces metabolic and mitochondrial compromise

    PubMed Central

    Sahin, Ergün; Colla, Simona; Liesa, Marc; Moslehi, Javid; Müller, Florian L.; Guo, Mira; Cooper, Marcus; Kotton, Darrell; Fabian, Attila J.; Walkey, Carl; Maser, Richard S.; Tonon, Giovanni; Foerster, Friedrich; Xiong, Robert; Wang, Y. Alan; Shukla, Sachet A.; Jaskelioff, Mariela; Martin, Eric S.; Heffernan, Timothy P.; Protopopov, Alexei; Ivanova, Elena; Mahoney, John E.; Kost-Alimova, Maria; Perry, Samuel R.; Bronson, Roderick; Liao, Ronglih; Mulligan, Richard; Shirihai, Orian S.; Chin, Lynda; DePinho, Ronald A.

    2013-01-01

    Telomere dysfunction activates p53-mediated cellular growth arrest, senescence and apoptosis to drive progressive atrophy and functional decline in high-turnover tissues. The broader adverse impact of telomere dysfunction across many tissues including more quiescent systems prompted transcriptomic network analyses to identify common mechanisms operative in haematopoietic stem cells, heart and liver. These unbiased studies revealed profound repression of peroxisome proliferator-activated receptor gamma, coactivator 1 alpha and beta (PGC-1α and PGC-1β, also known as Ppargc1a and Ppargc1b, respectively) and the downstream network in mice null for either telomerase reverse transcriptase (Tert) or telomerase RNA component (Terc) genes. Consistent with PGCs as master regulators of mitochondrial physiology and metabolism, telomere dysfunction is associated with impaired mitochondrial biogenesis and function, decreased gluconeogenesis, cardiomyopathy, and increased reactive oxygen species. In the setting of telomere dysfunction, enforced Tert or PGC-1α expression or germline deletion of p53 (also known as Trp53) substantially restores PGC network expression, mitochondrial respiration, cardiac function and gluconeogenesis. We demonstrate that telomere dysfunction activates p53 which in turn binds and represses PGC-1α and PGC-1β promoters, thereby forging a direct link between telomere and mitochondrial biology. We propose that this telomere–p53–PGC axis contributes to organ and metabolic failure and to diminishing organismal fitness in the setting of telomere dysfunction. PMID:21307849

  4. Diagnosis of erectile dysfunction.

    PubMed

    Glina, Sidney; Cohen, David J; Vieira, Marcelo

    2014-11-01

    Erectile dysfunction is a very prevalent condition and impairs quality of life of men and their partners. The diagnosis strategy of erectile dysfunction has changed, and it is important for every health professional to learn how to deal with erectile dysfunction. Although very prevalent, the sexual dysfunctions, including erectile dysfunction, continue to be underdiagnosed. Patients often expect physicians to initiate the conversation and ask about their troubles having sex. The routine to identify erectile dysfunction causes has undergone significant changes over the last decade. Identification of erectile dysfunction can be made through questionnaires or a complete medical and sexual history. Anamnesis and laboratory tests are sufficient in most cases to identify erectile dysfunction and to manage the treatment. Supplementary tests are used in special cases or when there is a need for an etiological diagnosis. Sexual function must be a part of every medical consultation, as any other body function. Erectile dysfunction diagnosis is not a complex task and can be accomplished by any physician. Even when the professional does not feel secure to treat erectile dysfunction, he or she can just identify the dysfunction and refer the patient to an expert.

  5. Distinct cytoprotective roles of pyruvate and ATP by glucose metabolism on epithelial necroptosis and crypt proliferation in ischaemic gut.

    PubMed

    Huang, Ching-Ying; Kuo, Wei-Ting; Huang, Chung-Yen; Lee, Tsung-Chun; Chen, Chin-Tin; Peng, Wei-Hao; Lu, Kuo-Shyan; Yang, Chung-Yi; Yu, Linda Chia-Hui

    2017-01-15

    Intestinal ischaemia causes epithelial death and crypt dysfunction, leading to barrier defects and gut bacteria-derived septic complications. Enteral glucose protects against ischaemic injury; however, the roles played by glucose metabolites such as pyruvate and ATP on epithelial death and crypt dysfunction remain elusive. A novel form of necrotic death that involves the assembly and phosphorylation of receptor interacting protein kinase 1/3 complex was found in ischaemic enterocytes. Pyruvate suppressed epithelial cell death in an ATP-independent manner and failed to maintain crypt function. Conversely, replenishment of ATP partly restored crypt proliferation but had no effect on epithelial necroptosis in ischaemic gut. Our data argue against the traditional view of ATP as the main cytoprotective factor by glucose metabolism, and indicate a novel anti-necroptotic role of glycolytic pyruvate under ischaemic stress. Mesenteric ischaemia/reperfusion induces epithelial death in both forms of apoptosis and necrosis, leading to villus denudation and gut barrier damage. It remains unclear whether programmed cell necrosis [i.e. receptor-interacting protein kinase (RIP)-dependent necroptosis] is involved in ischaemic injury. Previous studies have demonstrated that enteral glucose uptake by sodium-glucose transporter 1 ameliorated ischaemia/reperfusion-induced epithelial injury, partly via anti-apoptotic signalling and maintenance of crypt proliferation. Glucose metabolism is generally assumed to be cytoprotective; however, the roles played by glucose metabolites (e.g. pyruvate and ATP) on epithelial cell death and crypt dysfunction remain elusive. The present study aimed to investigate the cytoprotective effects exerted by distinct glycolytic metabolites in ischaemic gut. Wistar rats subjected to mesenteric ischaemia were enterally instilled glucose, pyruvate or liposomal ATP. The results showed that intestinal ischaemia caused RIP1-dependent epithelial necroptosis and

  6. Bacterial Vaginosis

    MedlinePlus

    ... Listen Español Text Size Email Print Share Bacterial Vaginosis Page Content Bacterial vaginosis (BV) is the most common vaginal infection in ... in harmful bacteria. The actual organism responsible for vaginosis hasn’t been clearly identified. BV is uncommon ...

  7. Burden of Sexual Dysfunction.

    PubMed

    Balon, Richard

    2017-01-02

    Similar to the burden of other diseases, the burden of sexual dysfunction has not been systematically studied. However, there is growing evidence of various burdens (e.g., economic, symptomatic, humanistic) among patients suffering from sexual dysfunctions. The burden of sexual dysfunction has been studied a bit more often in men, namely the burden of erectile dysfunction (ED), premature ejaculation (PE) and testosterone deficiency syndrome (TDS). Erectile dysfunction is frequently associated with chronic conditions such as cardiovascular disease, diabetes, and depression. These conditions could go undiagnosed, and ED could be a marker of those diseases. The only available report from the United Kingdom estimated the total economic burden of ED at £53 million annually in terms of direct costs and lost productivity. The burden of PE includes significant psychological distress: anxiety, depression, lack of sexual confidence, poor self-esteem, impaired quality of life, and interpersonal difficulties. Some suggest that increase in female sexual dysfunction is associated with partner's PE, in addition to significant interpersonal difficulties. The burden of TDS includes depression, sexual dysfunction, mild cognitive impairment, and osteoporosis. One UK estimate of the economic burden of female sexual dysfunctions demonstrated that the average cost per patient was higher than the per annum cost of ED. There are no data on burden of paraphilic disorders. The burden of sexual dysfunctions is underappreciated and not well studied, yet it is significant for both the patients and the society.

  8. Implications of mitochondrial DNA mutations and mitochondrial dysfunction in tumorigenesis

    PubMed Central

    Lu, Jianxin; Sharma, Lokendra Kumar; Bai, Yidong

    2016-01-01

    Alterations in oxidative phosphorylation resulting from mitochondrial dysfunction have long been hypothesized to be involved in tumorigenesis. Mitochondria have recently been shown to play an important role in regulating both programmed cell death and cell proliferation. Furthermore, mitochondrial DNA (mtDNA) mutations have been found in various cancer cells. However, the role of these mtDNA mutations in tumorigenesis remains largely unknown. This review focuses on basic mitochondrial genetics, mtDNA mutations and consequential mitochondrial dysfunction associated with cancer. The potential molecular mechanisms, mediating the pathogenesis from mtDNA mutations and mitochondrial dysfunction to tumorigenesis are also discussed. PMID:19532122

  9. Nuclear Proliferation Challenges

    SciTech Connect

    Professor William Potter

    2005-11-28

    William C. Potter, Director of the Center for Non Proliferation Studies and the Center for Russian and Eurasian Studies at the Monterey Institute of International Studies, will present nuclear proliferation challenges following the 2005 Nuclear Non-Proliferation Treaty (NPT) Review Conference. In addition to elucidating reasons for, and implications of, the conference’s failure, Dr. Potter will discuss common ground between nuclear proliferation and terrorism issues and whether corrective action can be taken.

  10. Endothelial dysfunction in rheumatic autoimmune diseases.

    PubMed

    Murdaca, Giuseppe; Colombo, Barbara Maria; Cagnati, Paola; Gulli, Rossella; Spanò, Francesca; Puppo, Francesco

    2012-10-01

    Rheumatic autoimmune diseases have been associated with accelerated atherosclerosis and various types of vasculopathies. Atherosclerosis is an inflammatory condition which starts as a "response to injury" favoring endothelial dysfunction which is associated with increased expression of adhesion molecules, pro-inflammatory cytokines, pro-thrombotic factors, oxidative stress upregulation and abnormal vascular tone modulation. Endothelial dysfunction in rheumatic autoimmune diseases involves innate immune responses, including macrophages and dendritic cells expression of scavenger and toll-like receptors for modified or native LDL as well as neutrophil and complement activation, and dysregulation of adaptive immune responses, including proliferation of autoreactive T-helper-1 lymphocytes and defective function of dendritic and regulatory T cells. Specific differences for endothelial function among different disorders include: a) increased amounts of pro-atherogenic hormones, decreased amounts of anti-atherogenic hormones and increased insulin resistance in rheumatoid arthritis; b) autoantibodies production in systemic lupus erythematosus and antiphospholipid syndrome; c) smooth muscle cells proliferation, destruction of internal elastic lamina, fibrosis and coagulation and fibrinolytic system dysfunction in systemic sclerosis. Several self-antigens (i.e. high density lipoproteins, heat shock proteins, β2-glycoprotein1) and self-molecules modified by oxidative events (i.e. low density lipoproteins and oxidized hemoglobin) have been identified as targets of autoimmune responses. Endothelial dysfunction leads to accelerated atherosclerosis in rheumatoid arthritis, systemic lupus erythematosus and spondyloarthropaties whereas obliterative vasculopathy is associated with systemic sclerosis. In this paper, we will briefly review the most relevant information upon endothelial dysfunction and inflammatory mechanisms in atherosclerosis and we will summarize the similarities

  11. Bacterial infections in cirrhosis.

    PubMed

    Garcia-Tsao, Guadalupe

    2004-06-01

    Hospitalized patients with cirrhosis are at increased risk of developing bacterial infections, the most common being spontaneous bacterial peritonitis (SBP) and urinary tract infections. Independent predictors of the development of bacterial infections in hospitalized cirrhotic patients are poor liver synthetic function and admission for gastrointestinal hemorrhage. Short term (seven-day) prophylaxis with norfloxacin reduces the rate of infections and improves survival and should therefore be administered to all patients with cirrhosis and variceal hemorrhage. Cirrhotic patients who develop abdominal pain, tenderness, fever, renal failure or hepatic encephalopathy should undergo diagnostic paracentesis, and those who meet the criterion for SBP (eg, an ascites neutrophil count greater than 250/mm3) should receive antibiotics, preferably a third-generation cephalosporin. In addition to antibiotic therapy, albumin infusions have been shown to reduce the risk of renal failure and mortality in patients with SBP, particularly in those with renal dysfunction and hyperbilirubinemia at the time of diagnosis. Patients who recover from an episode of SBP should be given long term prophylaxis with norfloxacin and should be assessed for liver transplantation.

  12. Erectile dysfunction: management update

    PubMed Central

    Fazio, Luke; Brock, Gerald

    2004-01-01

    DRAMATIC ADVANCES IN THE MANAGEMENT of erectile dysfunction have occurred over the past decade. Oral therapy with vasoactive agents has emerged as first-line treatment and has transformed both the manner in which the public views erectile dysfunction and the way health care providers deliver care. Whereas an extensive investigation was previously common in the management of erectile dysfunction, recent treatment guidelines promote a more minimalist, goal-oriented approach. In this article, we review the physiology of erection, and the pathophysiology, diagnosis and clinical management of erectile dysfunction. We also present the existing evidence for the efficacy of 3 phosphodiesterase inhibitors, the most widely used class of agents for erectile dysfunction. PMID:15111479

  13. Bacterial endophthalmitis.

    PubMed

    Durand, Marlene L

    2009-07-01

    Endophthalmitis refers to bacterial or fungal infection of the vitreous and/or aqueous humors of the eye. Bacterial endophthalmitis occurs most commonly after eye surgery or penetrating ocular trauma (exogenous endophthalmitis), but may also occur from hematogenous seeding during bacteremia (endogenous endophthalmitis). The presentation is usually acute, with eye pain and decreased vision. In exogenous endophthalmitis, infection is confined to the eye. There is no fever and minimal, if any, peripheral leukocytosis. Treatment includes direct injection of antibiotics into the vitreous, and vitrectomy in more severe cases. Systemic antibiotics are indicated in endogenous endophthalmitis; their role in exogenous endophthalmitis is controversial. Visual outcome depends on the virulence of the bacterial pathogen and the speed with which treatment is given. Acute bacterial endophthalmitis is a medical emergency, because delay in treatment may result in vision loss.

  14. [Bacterial vaginosis].

    PubMed

    Ostaszewska-Puchalska, Iwona; Zdrodowska-Stefanow, Bozena; Puciło, Katarzyna

    2004-09-01

    Bacterial vaginosis (BV) is one of the most common lower genital tract infections among women of childbearing age. This paper is a survey of literature data concerning epidemiology, pathogenesis, clinical and laboratory diagnostic criteria of this clinical syndrome.

  15. Cardiovascular Implications of Erectile Dysfunction

    MedlinePlus

    ... Heart Association Cardiology Patient Page Cardiovascular Implications of Erectile Dysfunction Bryan G. Schwartz , Robert A. Kloner Download PDF ... if you think you have ED. What Is Erectile Dysfunction? Erectile dysfunction means that a man is not ...

  16. Endothelial dysfunction: a comprehensive appraisal

    PubMed Central

    Esper, Ricardo J; Nordaby, Roberto A; Vilariño, Jorge O; Paragano, Antonio; Cacharrón, José L; Machado, Rogelio A

    2006-01-01

    The endothelium is a thin monocelular layer that covers all the inner surface of the blood vessels, separating the circulating blood from the tissues. It is not an inactive organ, quite the opposite. It works as a receptor-efector organ and responds to each physical or chemical stimulus with the release of the correct substance with which it may maintain vasomotor balance and vascular-tissue homeostasis. It has the property of producing, independently, both agonistic and antagonistic substances that help to keep homeostasis and its function is not only autocrine, but also paracrine and endocrine. In this way it modulates the vascular smooth muscle cells producing relaxation or contraction, and therefore vasodilatation or vasoconstriction. The endothelium regulating homeostasis by controlling the production of prothrombotic and antithrombotic components, and fibrynolitics and antifibrynolitics. Also intervenes in cell proliferation and migration, in leukocyte adhesion and activation and in immunological and inflammatory processes. Cardiovascular risk factors cause oxidative stress that alters the endothelial cells capacity and leads to the so called endothelial "dysfunction" reducing its capacity to maintain homeostasis and leads to the development of pathological inflammatory processes and vascular disease. There are different techniques to evaluate the endothelium functional capacity, that depend on the amount of NO produced and the vasodilatation effect. The percentage of vasodilatation with respect to the basal value represents the endothelial functional capacity. Taking into account that shear stress is one of the most important stimulants for the synthesis and release of NO, the non-invasive technique most often used is the transient flow-modulate "endothelium-dependent" post-ischemic vasodilatation, performed on conductance arteries such as the brachial, radial or femoral arteries. This vasodilatation is compared with the vasodilatation produced by drugs that

  17. Bacterial rheotaxis.

    PubMed

    Marcos; Fu, Henry C; Powers, Thomas R; Stocker, Roman

    2012-03-27

    The motility of organisms is often directed in response to environmental stimuli. Rheotaxis is the directed movement resulting from fluid velocity gradients, long studied in fish, aquatic invertebrates, and spermatozoa. Using carefully controlled microfluidic flows, we show that rheotaxis also occurs in bacteria. Excellent quantitative agreement between experiments with Bacillus subtilis and a mathematical model reveals that bacterial rheotaxis is a purely physical phenomenon, in contrast to fish rheotaxis but in the same way as sperm rheotaxis. This previously unrecognized bacterial taxis results from a subtle interplay between velocity gradients and the helical shape of flagella, which together generate a torque that alters a bacterium's swimming direction. Because this torque is independent of the presence of a nearby surface, bacterial rheotaxis is not limited to the immediate neighborhood of liquid-solid interfaces, but also takes place in the bulk fluid. We predict that rheotaxis occurs in a wide range of bacterial habitats, from the natural environment to the human body, and can interfere with chemotaxis, suggesting that the fitness benefit conferred by bacterial motility may be sharply reduced in some hydrodynamic conditions.

  18. Bacterial vaginosis.

    PubMed

    Weaver, C H; Mengel, M B

    1988-08-01

    Bacterial vaginosis (nonspecific vaginitis) is a polymicrobial, superficial vaginal infection caused by an increase in anaerobic organisms and a concomitant decrease in lactobacilli. Gardnerella vaginalis, once thought to be the sole etiologic agent, is probably one of several endogenous members of the vaginal flora that overgrow in women with bacterial vaginosis. Whether the growth of anaerobes or a primary decrease in lactobacilli is the initial pathogenic event remains unclear. Epidemiological studies have revealed that current or previous infections caused by Trichomonas organisms, increased sexual activity, and intrauterine device use are risk factors for this condition. Studies have indicated that bacterial vaginosis, previously thought to be a benign illness, is associated with some morbidity in pregnant women. Symptoms remain unreliable in the diagnosis of bacterial vaginosis. Diagnostic efficacy is best achieved by utilizing clinical signs. Assessment of cure is best accomplished by Gram stain, not clinical criteria. Metronidazole, 500 mg orally for seven days, remains the treatment of choice; however, a 2-g single dose of metronidazole represents a reasonable alternative if cost and compliance issues predominate in a clinical situation. Although a recent study supports the contention that treatment of the male sexual partner of women with bacterial vaginosis is effective, a general recommendation cannot be made with confidence on the issue of sexual partner treatment until other supporting work is done.

  19. Bacterial conjunctivitis

    PubMed Central

    2012-01-01

    Introduction Most cases of conjunctivitis in adults are probably due to viral infection, but children are more likely to develop bacterial conjunctivitis than they are viral forms. The main bacterial pathogens are Haemophilus influenzae and Streptococcus pneumoniae in adults and children, and Moraxella catarrhalis in children. Contact lens wearers may be more likely to develop gram-negative infections. Bacterial keratitis occurs in up to 30 per 100,000 contact lens wearers. Methods and outcomes We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of empirical treatment in adults and children with suspected bacterial conjunctivitis? What are the effects of treatment in adults and children with bacteriologically confirmed bacterial conjunctivitis? What are the effects of treatment in adults and children with clinically confirmed gonococcal conjunctivitis? We searched: Medline, Embase, The Cochrane Library, and other important databases up to July 2011 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). Results We found 44 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. Conclusions In this systematic review we present information relating to the effectiveness and safety of the following interventions: ocular decongestants, oral antibiotics, parenteral antibiotics, saline, topical antibiotics, and warm compresses. PMID:22348418

  20. Bacterial conjunctivitis.

    PubMed

    Epling, John

    2012-02-20

    Most cases of conjunctivitis in adults are probably due to viral infection, but children are more likely to develop bacterial conjunctivitis than they are viral forms. The main bacterial pathogens are Haemophilus influenzae and Streptococcus pneumoniae in adults and children, and Moraxella catarrhalis in children. Contact lens wearers may be more likely to develop gram-negative infections. Bacterial keratitis occurs in up to 30 per 100,000 contact lens wearers. We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of empirical treatment in adults and children with suspected bacterial conjunctivitis? What are the effects of treatment in adults and children with bacteriologically confirmed bacterial conjunctivitis? What are the effects of treatment in adults and children with clinically confirmed gonococcal conjunctivitis? We searched: Medline, Embase, The Cochrane Library, and other important databases up to July 2011 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). We found 44 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. In this systematic review we present information relating to the effectiveness and safety of the following interventions: ocular decongestants, oral antibiotics, parenteral antibiotics, saline, topical antibiotics, and warm compresses.

  1. Bacterial rheotaxis

    PubMed Central

    Marcos; Fu, Henry C.; Powers, Thomas R.; Stocker, Roman

    2012-01-01

    The motility of organisms is often directed in response to environmental stimuli. Rheotaxis is the directed movement resulting from fluid velocity gradients, long studied in fish, aquatic invertebrates, and spermatozoa. Using carefully controlled microfluidic flows, we show that rheotaxis also occurs in bacteria. Excellent quantitative agreement between experiments with Bacillus subtilis and a mathematical model reveals that bacterial rheotaxis is a purely physical phenomenon, in contrast to fish rheotaxis but in the same way as sperm rheotaxis. This previously unrecognized bacterial taxis results from a subtle interplay between velocity gradients and the helical shape of flagella, which together generate a torque that alters a bacterium's swimming direction. Because this torque is independent of the presence of a nearby surface, bacterial rheotaxis is not limited to the immediate neighborhood of liquid–solid interfaces, but also takes place in the bulk fluid. We predict that rheotaxis occurs in a wide range of bacterial habitats, from the natural environment to the human body, and can interfere with chemotaxis, suggesting that the fitness benefit conferred by bacterial motility may be sharply reduced in some hydrodynamic conditions. PMID:22411815

  2. Sexual Dysfunction in Women

    MedlinePlus

    ... pressure), excessive alcohol use or vaginal infections can cause sexual problems. Depression, relationship problems or abuse (current or past abuse) can also cause sexual dysfunction.You may have less sexual desire ...

  3. Distal median nerve dysfunction

    MedlinePlus

    ... Distal median nerve dysfunction is a form of peripheral neuropathy that affects the movement of or sensation in ... and the A.D.A.M. Editorial team. Peripheral Nerve Disorders Read more Latest Health News Read more Health ...

  4. Temporomandibular Joint Dysfunction

    MedlinePlus

    The temporomandibular joint (TMJ) connects your jaw to the side of your head. When it works well, it enables you to ... For people with TMJ dysfunction, problems with the joint and muscles around it may cause Pain that ...

  5. Chronic pelvic floor dysfunction.

    PubMed

    Hartmann, Dee; Sarton, Julie

    2014-10-01

    The successful treatment of women with vestibulodynia and its associated chronic pelvic floor dysfunctions requires interventions that address a broad field of possible pain contributors. Pelvic floor muscle hypertonicity was implicated in the mid-1990s as a trigger of major chronic vulvar pain. Painful bladder syndrome, irritable bowel syndrome, fibromyalgia, and temporomandibular jaw disorder are known common comorbidities that can cause a host of associated muscular, visceral, bony, and fascial dysfunctions. It appears that normalizing all of those disorders plays a pivotal role in reducing complaints of chronic vulvar pain and sexual dysfunction. Though the studies have yet to prove a specific protocol, physical therapists trained in pelvic dysfunction are reporting success with restoring tissue normalcy and reducing vulvar and sexual pain. A review of pelvic anatomy and common findings are presented along with suggested physical therapy management. Copyright © 2014 Elsevier Ltd. All rights reserved.

  6. Ocular surface microbiome in meibomian gland dysfunction.

    PubMed

    Watters, Grant A; Turnbull, Philip R; Swift, Simon; Petty, Alex; Craig, Jennifer P

    2017-03-01

    To investigate the ocular microbiome in meibomian gland dysfunction in Auckland, New Zealand. Prospective, cross-sectional, observational, university-based study. Participants resident in New Zealand for ≥2 years (n = 157) were classified as normal (n = 66), mild (n = 41) or moderate-to-severe meibomian gland dysfunction (n = 50). Contact lens wear and anterior blepharitis status were recorded, as well as symptoms and clinical features. Bacteria collected from lid margin swabs, before and after gland expression, were isolated and identified by conventional microbiological culture techniques. Aerobic isolates were identified in all 157 participants, and both aerobic and anaerobic bacteria isolated in a subset of 87 subjects. Bacterial incidence according to meibomian gland dysfunction status RESULTS: Symptoms, bulbar hyperaemia, conjunctival staining, lipid layer grade and tear film stability, but not corneal staining, showed moderate association with meibomian gland dysfunction severity. Participants with and without meibomian gland dysfunction showed a similar microbiome, unaffected by gland expression. Anterior blepharitis, a common co-morbidity, was not an independent predictor of the microbiome. Sterile cultures were more common in contact lens wearers than non-wearers. The incidence of Staphylococcus aureus was higher than anticipated across all severity groups, and that of coagulase-negative Staphylococcus, Corynebacterium and streptococci was lower. Modest differences in relative proportions of bacteria compared with other studies support climatic variations in the ocular surface microbiome. Similarity in microbiome profile, irrespective of meibomian gland dysfunction severity, anterior blepharitis presence or contact lens wear, suggests potential for commonality in treatment. © 2016 Royal Australian and New Zealand College of Ophthalmologists.

  7. [Beyond immunopathogenesis. Insulin resistance and "epidermal dysfunction"].

    PubMed

    Boehncke, W-H; Boehncke, S; Buerger, C

    2012-03-01

    Insulin is a central player in the regulation of metabolic as well as non-metabolic cells: inefficient signal transduction (insulin resistance) not only represents the cornerstone in the pathogenesis of type 2 diabetes mellitus, but also drives atherosclerosis through inducing endothelial dysfunction. Last but not least epidermal homeostasis depends on insulin. We summarize the effects of insulin on proliferation and differentiation of human keratinocytes as well as the relevance of cytokine-induced insulin resistance for alterations in epidermal homeostasis characteristic for psoriasis. Kinases involved in both insulin- as well as cytokine-receptor signaling represent potential targets for innovative therapeutics. Such small molecules would primarily normalize "epidermal dysfunction", thus complementing the immunomodulatory strategies of today's biologics.

  8. Sexual Dysfunction in Women

    PubMed Central

    Brown, Pamela

    1989-01-01

    Sexual dysfunction takes place in the context of women's lives and affects their sexuality and self-esteem. Awareness of these influences are vital to the management of the dysfunction and the promotion of positive sexuality. The family physician's contribution to both the prevention and management of sexual concerns includes an awareness of societal influences and facilitation of a woman's sense of her own power and control over her life. PMID:21248971

  9. Mitochondrial Dysfunction in Depression

    PubMed Central

    Bansal, Yashika; Kuhad, Anurag

    2016-01-01

    Abstract: Background Depression is the most debilitating neuropsychiatric disorder with significant impact on socio-occupational and well being of individual. The exact pathophysiology of depression is still enigmatic though various theories have been put forwarded. There are evidences showing that mitochondrial dysfunction in various brain regions is associated with depression. Recent findings have sparked renewed appreciation for the role of mitochondria in many intracellular processes coupled to synaptic plasticity and cellular resilience. New insights in depression pathophysiology are revolving around the impairment of neuroplasticity. Mitochondria have potential role in ATP production, intracellular Ca2+ signalling to establish membrane stability, reactive oxygen species (ROS) balance and to execute the complex processes of neurotransmission and plasticity. So understanding the various concepts of mitochondrial dysfunction in pathogenesis of depression indubitably helps to generate novel and more targeted therapeutic approaches for depression treatment. Objective The review was aimed to give a comprehensive insight on role of mitochondrial dysfunction in depression. Result Targeting mitochondrial dysfunction and enhancing the mitochondrial functions might act as potential target for the treatment of depression. Conclusion Literature cited in this review highly supports the role of mitochondrial dysfunction in depression. As impairment in the mitochondrial functions lead to the generation of various insults that exaggerate the pathogenesis of depression. So, it is useful to study mitochondrial dysfunction in relation to mood disorders, synaptic plasticity, neurogenesis and enhancing the functions of mitochondria might show promiscuous effects in the treatment of depressed patients. PMID:26923778

  10. Neutrophil Dysfunction in Sepsis

    PubMed Central

    Zhang, Fang; Liu, An-Lei; Gao, Shuang; Ma, Shui; Guo, Shu-Bin

    2016-01-01

    Objective: Sepsis is defined as life-threatening organ dysfunction due to a dysregulated host response to infection. In this article, we reviewed the correlation between neutrophil dysfunction and sepsis. Data Sources: Articles published up to May 31, 2016, were selected from the PubMed databases, with the keywords of “neutrophil function”, “neutrophil dysfunction”, and “sepsis”. Study Selection: Articles were obtained and reviewed to analyze the neutrophil function in infection and neutrophil dysfunction in sepsis. Results: We emphasized the diagnosis of sepsis and its limitations. Pathophysiological mechanisms involve a generalized circulatory, immune, coagulopathic, and/or neuroendocrine response to infection. Many studies focused on neutrophil burst or cytokines. Complement activation, impairment of neutrophil migration, and endothelial lesions are involved in this progress. Alterations of cytokines, chemokines, and other mediators contribute to neutrophil dysfunction in sepsis. Conclusions: Sepsis represents a severe derangement of the immune response to infection, resulting in neutrophil dysfunction. Neutrophil dysfunction promotes sepsis and even leads to organ failure. Mechanism studies, clinical practice, and strategies to interrupt dysregulated neutrophil function in sepsis are desperately needed. PMID:27824008

  11. Renal dysfunction in cirrhosis

    PubMed Central

    Urrunaga, Nathalie H.; Mindikoglu, Ayse L.; Rockey, Don C.

    2015-01-01

    Purpose of review Renal dysfunction causes significant morbidity in cirrhotic patients. Diagnosis is challenging because it is based on serum creatinine, which is used to calculate estimated glomerular filtration rate, which itself is not an ideal measure of renal function in patients with cirrhosis. Finding the exact cause of renal injury in patients with cirrhosis remains problematic due to the limitations of the current diagnostic tests. The purpose of this review is to highlight studies used to diagnose renal dysfunction in patients with renal dysfunction and review current treatments. Recent findings New diagnostic criteria and classification of renal dysfunction, especially for acute kidney injury (AKI), have been proposed in hopes of optimizing treatment and improving outcomes. New biomarkers that help to differentiate structural from functional AKI in cirrhotic patients have been developed, but require further investigation. Vasoconstrictors are the most commonly recommended treatment of hepatorenal syndrome (HRS). Given the high mortality in patients with type 1 HRS, all patients with HRS should be evaluated for liver transplantation. When renal dysfunction is considered irreversible, combined liver–kidney transplantation is advised. Summary Development of new biomarkers to differentiate the different types of AKI in cirrhosis holds promise. Early intervention in cirrhotic patients with renal dysfunction offers the best hope of improving outcomes. PMID:25763790

  12. Effect of Vibration on Bacterial Growth and Antibiotic Resistance

    NASA Technical Reports Server (NTRS)

    Juergensmeyer, Elizabeth A.; Juergensmeyer, Margaret A.

    2004-01-01

    The purpose of this research grant was to provide a fundamental, systematic investigation of the effects of oscillatory acceleration on bacterial proliferation and their responses to antibiotics in a liquid medium.

  13. Bacterial Tracheitis

    MedlinePlus

    ... Nears (News) Vaccination 101: Make Sure Kids Are Up to Date Additional Content Medical News Bacterial Tracheitis By Rajeev ... News HealthDay Vaccination 101: Make Sure Kids Are Up to Date MONDAY, Aug. 28, 2017 (HealthDay News) -- As the ...

  14. PGC-1α, Mitochondrial Dysfunction and Huntington’s Disease

    PubMed Central

    Johri, Ashu; Chandra, Abhishek; Beal, M. Flint

    2013-01-01

    The constant high energy demand of neurons makes them rely heavily on their mitochondria. Dysfunction of mitochondrial energy metabolism leads to reduced ATP production, impaired calcium buffering, and generation of reactive oxygen species. There is strong evidence that mitochondrial dysfunction results in neurodegeneration and may contribute to the pathogenesis of Huntington’s disease (HD). Studies over the past few years have implicated an impaired function of peroxisome proliferator-activated receptor (PPAR)-γ coactivator-1α (PGC-1α), a transcriptional master co-regulator of mitochondrial biogenesis, metabolism and antioxidant defenses, in causing mitochondrial dysfunction in HD. Here we have attempted to discuss in a nutshell, the key findings on the role of PGC-1α in mitochondrial dysfunction in HD and its potential as a therapeutic target to cure HD. PMID:23602910

  15. Neurogenic voiding dysfunction.

    PubMed

    Georgopoulos, Petros; Apostolidis, Apostolos

    2017-05-01

    This review aims to analyze and discuss all recently published articles associated with neurogenic voiding discussion providing readers with the most updated knowledge and trigger for further research. They include the proposal of a novel classification system for the pathophysiology of neurogenic lower urinary tract dysfunction (NLUTD) which combines neurological defect in a distinct anatomic location, and data on bowel dysfunction, autonomic dysreflexia and urine biomarkers; review of patient-reported outcome measures in NLUTD; review of the criteria for the diagnosis of clinically significant urinary infections; novel research findings on the pathophysiology of NLUTD; and review of data on minimally and more invasive treatments. Despite the extended evidence base on NLUTD, there is a paucity of high-quality new research concerning voiding dysfunction as opposed to storage problems. The update aims to inform clinicians about new developments in clinical practice, as well as ignite discussion for further clinical and basic research in the aforementioned areas of NLUTD.

  16. Diastolic dysfunction in hypertension.

    PubMed

    Nazário Leão, R; Marques da Silva, P

    2017-03-03

    Hypertension and coronary heart disease, often coexisting, are the most common risk factors for heart failure. The progression of hypertensive heart disease involves myocardial fibrosis and alterations in the left ventricular geometry that precede the functional change, initially asymptomatic. The left ventricular diastolic dysfunction is part of this continuum being defined by the presence of left ventricular diastolic dysfunction without signs or symptoms of heart failure or poor left ventricular systolic function. It is highly prevalent in hypertensive patients and is associated with increased cardiovascular morbidity and mortality. Despite its growing importance in clinical practice it remains poorly understood. This review aims to present the epidemiological fundamentals and the latest developments in the pathophysiology, diagnosis and treatment of left ventricular diastolic dysfunction.

  17. Bacterial cryotomography

    NASA Astrophysics Data System (ADS)

    Jensen, Grant

    2009-03-01

    Electron cryotomography (ECT) is an emerging technique that allows thin samples such as small cells, viruses, or tissue sections to be imaged in 3-D in a near-native, ``frozen-hydrated'' state to molecular (˜4 nm) resolution. Thus ECT fills a critical gap between light microscopy and higher resolution structural techniques like X-ray crystallography and NMR. In a combination of technology development and biological application, during the past few years our lab has been studying bacterial ultrastructure through ECT of intact, plunge-frozen cells. We have now collected over a thousand tomograms of more than ten different species. This work has revealed the surprising complexity of the bacterial cytoskeleton as well as the architectures of several important ``supramolecular'' complexes including the chemoreceptor array, the flagellar motor, and the cell wall peptidoglycan. Example results highlighting both the potential and limitations of this technology will be shown.

  18. Male endocrine dysfunction.

    PubMed

    Hotaling, James M; Patel, Zamip

    2014-02-01

    Evaluation for endocrine function is a pivotal part of the male infertility workup. Endocrine dysfunction may result from endogenous and exogenous sources. This article describes the traditional roles that the hypothalamic-pituitary-gonadal endocrine axis plays in spermatogenesis and testicular dysfunction, as well as other insults that may contribute to hypospermatogenesis. Recent research into the role alternative hormonal axes play in spermatogenesis and promising new technologies that may correct inborn or acquired endocrinopathies leading to impaired sperm growth and maturation are discussed. Copyright © 2014 Elsevier Inc. All rights reserved.

  19. Bacterial cell biology outside the streetlight

    PubMed Central

    2016-01-01

    Summary As much as vertical transmission of microbial symbionts requires their deep integration into the host reproductive and developmental biology, symbiotic lifestyle might profoundly affect bacterial growth and proliferation. This review describes the reproductive oddities displayed by bacteria associated – more or less intimately – with multicellular eukaryotes. PMID:27306428

  20. [The effects of occluding dysfunction on marginal parodontopathies].

    PubMed

    Stănescu, S; Ispirescu, M; Ispirescu, D; Swoboda, M L

    1990-01-01

    Occluding dysfunction (occluding dysharmony, occluding trauma) is an important etiologic factor of parodontal disease. It is an integrating element of the destructive process which characterizes the parodontal disease. Occluding dysfunction does not trigger gingivitis, or the development of parodontal pouches, but it does exert an influence on the progress and the importance of parodontal pouches determined by local irritation due to tartar and to bacterial plaques. Occluding dysfunction and the inflammation of parodontal tissues are different processes which occur in the course of the same disease namely of marginal parodonthitis. The inflammation develops in the gums and propagates in the parodontal sustaining tissues. Occluding dysfunction (also known as occluding dysharmony or occluding trauma) occurs in the parodontal sustaining tissues, and both determine tissue destruction. Occluding dysfunction and inflammation become codestructive factors which are interconnected, and are both capable to determine clinical and radiologic changes which are typical for diseased marginal parodontium. Due to the fact that individuals have variable parodontal reactions to local irritation factors, and considering the fact that inflammation and occluding dysfunction occur together but with variable degrees of severity, it is possible that they will not determine in all cases intraosseus pouches with angular lesions, or crater-like lesions. However, when we are confronted with such lesions it is very likely that the combined effects of inflammation and occluding dysfunction are at the origin.

  1. Gastrointestinal dysfunction in idiopathic Parkinsonism: A narrative review

    PubMed Central

    Salari, Mehri; Fayyazi, Emad; Mirmosayyeb, Omid

    2016-01-01

    Currently, gastrointestinal (GI) dysfunctions in Parkinson's disease (PD) are well-recognized problems and are known to be the initial symptoms in the pathological process that eventually results in PD. Many types of PD-associated GI dysfunctions have been identified, including weight loss, nausea, hypersalivation, dysphagia, dyspepsia, abdominal pain, intestinal pseudo-obstruction, constipation, defecatory dysfunction, and small intestinal bacterial overgrowth. These symptoms can influence on other PD symptoms and are the second most significant predictor of the quality of life of these patients. Recognition of GI symptoms requires vigilance on the part of clinicians. Health-care providers should routinely ask direct questions about GI symptoms during office visits so that efforts can be directed at appropriate management of these distressing manifestations. Multiple system atrophy (MSA) and progressive supranuclear palsy are two forms of neurodegenerative Parkinsonism. Symptoms of autonomic dysfunctions such as GI dysfunction are common in patients with parkinsonian disorders. Despite recent progress in the recognition of GI dysfunctions, there are a few reviews on the management of GI dysfunction and GI symptoms in idiopathic Parkinsonism. In this review, the clinical presentation, pathophysiology, and treatment of each GI symptom in PD, MSA, and prostate-specific antigen will be discussed. PMID:28331512

  2. Female sexual dysfunction: Assessment.

    PubMed

    Sharma, J B; Kalra, Bharti

    2016-05-01

    Female sexual dysfunction (FSD) is a common complex clinical condition, with multiple etiologies, association and pathophysiologic correlations. This review includes the definition, etiology, and diagnosis of FSD. It calls for a bio psychosocial approach to FSD management, which incorporates, but is not limited to, only the psychological aspects of FSD.

  3. Perceptual-Motor Dysfunction.

    ERIC Educational Resources Information Center

    Pyfer, Jean L.

    Discussed are theoretical and treatment aspects of perceptual motor dysfunction and rehabilitation in 4- to 12-year-old academically failing children involved in a 3-year investigation at the University of Kansas. The program is said to stress increasing the amount of stimulation received by sensory receptors of the vestibular, reflex, and haptic…

  4. Multiple organ dysfunction syndrome.

    PubMed

    Parke, A L; Liu, P T; Parke, D V

    2003-01-01

    Multiple organ dysfunction syndrome, including acute respiratory distress syndrome (ARDS) and renal failure, is described, its clinical features outlined, its origins in tissue oxidative stress following severe infections, surgical trauma, ionizing radiation, high-dosage drugs and chemicals, severe hemorrhage, etc., are defined, and its prevention and treatment prescribed.

  5. Shared Parenting Dysfunction.

    ERIC Educational Resources Information Center

    Turkat, Ira Daniel

    2002-01-01

    Joint custody of children is the most prevalent court ordered arrangement for families of divorce. A growing body of literature indicates that many parents engage in behaviors that are incompatible with shared parenting. This article provides specific criteria for a definition of the Shared Parenting Dysfunction. Clinical aspects of the phenomenon…

  6. Adipocytokines in Thyroid Dysfunction

    PubMed Central

    Aydogan, Berna İmge; Sahin, Mustafa

    2013-01-01

    Adipocytokines are important mediators of interorgan crosstalk in metabolic regulation. Thyroid diseases have effects on metabolism and inflammation. The mechanism of these effects is not clear. Recently, there are several reports suggesting this interrelation between adipocytokines and thyroid dysfunction. In this review, we summarize this relation according to the literature. PMID:24049662

  7. [Bacterial vaginosis].

    PubMed

    Jesús De La Calle, Iría; Jesús De La Calle, M Antonia

    2009-11-28

    Bacterial vaginosis is a widely spread health problem with multiple connotations. It has been the subject of many studies and work during decades and it still remains a polemic entity, with contradictory finding. The polymicrobian etiology, unsolved epidemiology, obstetrico-gynecological complications and high recurrence rate following treatment, make this infection a target for researchers. It is not an inflammatory process -yet an immune response exists. In this disorder, vaginal discharge increases, and it is associated with a high risk of developing sexually transmitted diseases.

  8. What Is a Dysfunctional School?

    ERIC Educational Resources Information Center

    Bergman, M. M.

    2013-01-01

    Whether or not a school is dysfunctional depends largely on how dysfunctionality in schools is defined and measured. Dysfunctionality, as any construct, is subject to definition and interpretation, and it is thus always marked by perspectivism. But regardless of the definition games occasionally played by academics, some form of reality takes…

  9. What Is a Dysfunctional School?

    ERIC Educational Resources Information Center

    Bergman, M. M.

    2013-01-01

    Whether or not a school is dysfunctional depends largely on how dysfunctionality in schools is defined and measured. Dysfunctionality, as any construct, is subject to definition and interpretation, and it is thus always marked by perspectivism. But regardless of the definition games occasionally played by academics, some form of reality takes…

  10. The cone dysfunction syndromes

    PubMed Central

    Aboshiha, Jonathan; Dubis, Adam M; Hardcastle, Alison J; Michaelides, Michel

    2016-01-01

    The cone dysfunction syndromes are a heterogeneous group of inherited, predominantly stationary retinal disorders characterised by reduced central vision and varying degrees of colour vision abnormalities, nystagmus and photophobia. This review details the following conditions: complete and incomplete achromatopsia, blue-cone monochromatism, oligocone trichromacy, bradyopsia and Bornholm eye disease. We describe the clinical, psychophysical, electrophysiological and imaging findings that are characteristic to each condition in order to aid their accurate diagnosis, as well as highlight some classically held notions about these diseases that have come to be challenged over the recent years. The latest data regarding the genetic aetiology and pathological changes observed in the cone dysfunction syndromes are discussed, and, where relevant, translational avenues of research, including completed and anticipated interventional clinical trials, for some of the diseases described herein will be presented. Finally, we briefly review the current management of these disorders. PMID:25770143

  11. Prevalence of Sexual Dysfunctions

    PubMed Central

    Simons, Jeffrey; Carey, Michael P.

    2008-01-01

    Ten years of research that has provided data regarding the prevalence of sexual dysfunctions is reviewed. A thorough review of the literature identified 52 studies that have been published in the 10 years since an earlier review by Spector and Carey (1990). Community samples indicate a current prevalence of 0 - 3% for male orgasmic disorder, 0 - 5% for erectile disorder, and 0 - 3% for male hypoactive sexual desire disorder. Pooling current and 1-year figures provides community prevalence estimates of 7 - 10% for female orgasmic disorder and 4 - 5% for premature ejaculation. Stable community estimates of the current prevalence for the other sexual dysfunctions remain unavailable. Prevalence estimates obtained from primary care and sexuality clinic samples are characteristically higher. Although a relatively large number of studies have been conducted since Spector and Carey’s (1990) review, the lack of methodological rigor of many studies limits the confidence that can be placed in these findings. PMID:11329727

  12. Sexual dysfunction in diabetes.

    PubMed

    Tamás, Várkonyi; Kempler, Peter

    2014-01-01

    We aimed to summarize the etiology, clinical characteristics, diagnosis, and possible treatment options of sexual dysfunction in diabetic patients of both sexes. Details of dysfunction in diabetic women are less conclusive than in men due to the lack of standardized evaluation of sexual function in women. Male sexual dysfunction is a common complication of diabetes, including abnormalities of orgasmic/ejaculatory function and desire/libido in addition to penile erection. The prevalence of erectile dysfunction (ED) among diabetic men varies from 35% to 75%. Diabetes-induced ED has a multifactorial etiology including metabolic, neurologic, vascular, hormonal, and psychological components. ED should be regarded as the first sign of cardiovascular disease because it can be present before development of symptomatic coronary artery disease, as larger coronary vessels better tolerate the same amount of plaque compared to smaller penile arteries. The diagnosis of ED is based on validated questionnaires and determination of functional and organic abnormalities. First-, second- and third-line therapy may be applied. Phosphodiesterase-5 (PDE-5) inhibitor treatment from the first-line options leads to smooth muscle relaxation in the corpus cavernosum and enhancement in blood flow, resulting in erection during sexual stimulus. The use of PDE-5 inhibitors in the presence of oral nitrates is strictly contraindicated in diabetic men, as in nondiabetic subjects. All PDE-5 inhibitors have been evaluated for ED in diabetic patients with convincing efficacy data. Second-line therapy includes intracavernosal, trans- or intraurethral administration of vasoactive drugs or application of a vacuum device. Third-line therapies are the implantation of penile prosthesis and penile revascularization.

  13. Sexual Dysfunction After Urethroplasty.

    PubMed

    Dogra, Prem Nath; Singh, Prabhjot; Nayyar, Rishi; Yadav, Siddharth

    2017-02-01

    Posturethroplasty sexual dysfunction (SD) is multifactorial and its true incidence is unknown. Even with the current evidence suggesting that it is uncommon, de novo SD causes dissatisfaction even after a successful surgery. Posterior urethroplasty carries the highest chance of SD, mostly attributable to the pelvic fracture itself rather than the urethroplasty. With anterior urethroplasty, transecting bulbar urethroplasty leads to greater SD compared with penile or nontransecting bulbar urethroplasty. Most patients with posturethroplasty SD recover within 6 months after surgery.

  14. Thyroid dysfunction and subfertility.

    PubMed

    Cho, Moon Kyoung

    2015-12-01

    The thyroid hormones act on nearly every cell in the body. Moreover, the thyroid gland continuously interacts with the ovaries, and the thyroid hormones are involved in almost all phases of reproduction. Thyroid dysfunctions are relatively common among women of reproductive age, and can affect fertility in various ways, resulting in anovulatory cycles, high prolactin levels, and sex hormone imbalances. Undiagnosed and untreated thyroid disease can be a cause of subfertility. Subclinical hypothyroidism (SCH), also known as mild thyroid failure, is diagnosed when peripheral thyroid hormone levels are within the normal reference laboratory range, but serum thyroid-stimulating hormone levels are mildly elevated. Thyroid autoimmunity (TAI) is characterized by the presence of anti-thyroid antibodies, which include anti-thyroperoxidase and anti-thyroglobulin antibodies. SCH and TAI may remain latent, asymptomatic, or even undiagnosed for an extended period. It has also been demonstrated that controlled ovarian hyperstimulation has a significant impact on thyroid function, particularly in women with TAI. In the current review, we describe the interactions between thyroid dysfunctions and subfertility, as well as the proper work-up and management of thyroid dysfunctions in subfertile women.

  15. Diastolic dysfunction in hypertension.

    PubMed

    Slama, Michel; Susic, Dinko; Varagic, Jasmina; Frohlich, Edward D

    2002-07-01

    Heart failure is one of the most common causes of cardiovascular morbidity and mortality, and hypertension is the most common cause of cardiac failure. Recent studies have shown that isolated diastolic dysfunction very often accompanies hypertensive heart disease. Ventricular diastolic function may be divided into an active relaxation phase and a passive compliance period. These two components have been investigated invasively, and they remain the gold standards for the study of diastolic function. However, in the routine clinical setting, echocardiographic and Doppler techniques are most useful for evaluating ventricular filling. Thus, analysis of E and A waves of mitral flow have provided important and useful information. Unfortunately, these indices depend on too many factors. Newer indices obtained from ventricular time intervals, tissue Doppler imaging, and color M-mode echocardiography have enhanced the means to assess diastolic function. In addition, new methods including MRI and cine CT have also provided better understanding of left ventricular filling in hypertension. Using these techniques, diastolic dysfunction has been found to be common in patients with hypertension, even before left ventricular hypertrophy is demonstrable and before hypertension in young, normotensive male offspring of hypertensive parents has developed. Furthermore, it has been made clear recently that myocardial ischemia and fibrosis are two important factors associated with diastolic dysfunction in hypertension.

  16. Preclinical Diastolic Dysfunction

    PubMed Central

    Wan, Siu-Hin; Vogel, Mark W.; Chen, Horng H

    2014-01-01

    Preclinical Diastolic Dysfunction (PDD) has been broadly defined as subjects with left ventricular diastolic dysfunction, without the diagnosis of congestive heart failure (HF), and with normal systolic function. PDD is an entity which remains poorly understood, yet has definite clinical significance. Although few original studies have focused on PDD, it has been shown that PDD is prevalent, and that there is a clear progression from PDD to symptomatic heart failure including dyspnea, edema, and fatigue. In diabetic patients and patients with coronary artery disease or hypertension, it has been shown that patients with PDD have a significantly higher risk of progression to heart failure and death compared to patients without PDD. Because of these findings and the increasing prevalence of the heart failure epidemic, it is clear that an understanding of PDD is essential to decreasing patients’ morbidity and mortality. This review will focus on what is known concerning preclinical diastolic dysfunction, including definitions, staging, epidemiology, pathophysiology, and the natural history of the disease. In addition, given the paucity of trials focused on PDD treatment, studies targeting risk factors associated with the development of PDD and therapeutic trials for heart failure with preserved ejection fraction will be reviewed. PMID:24291270

  17. Bacterial Hydrodynamics

    NASA Astrophysics Data System (ADS)

    Lauga, Eric

    2016-01-01

    Bacteria predate plants and animals by billions of years. Today, they are the world's smallest cells, yet they represent the bulk of the world's biomass and the main reservoir of nutrients for higher organisms. Most bacteria can move on their own, and the majority of motile bacteria are able to swim in viscous fluids using slender helical appendages called flagella. Low-Reynolds number hydrodynamics is at the heart of the ability of flagella to generate propulsion at the micrometer scale. In fact, fluid dynamic forces impact many aspects of bacteriology, ranging from the ability of cells to reorient and search their surroundings to their interactions within mechanically and chemically complex environments. Using hydrodynamics as an organizing framework, I review the biomechanics of bacterial motility and look ahead to future challenges.

  18. Bacterial vaginosis.

    PubMed

    Priestley, C J; Kinghorn, G R

    1996-09-01

    Bacterial vaginosis (BV) is an alteration of the vaginal flora, where the normally predominant lactobacilli are replaced by a cocktail of organisms including Gardnerella vaginalis and anaerobes. It presents with a grey, homogenous, offensive vaginal discharge that has a raised pH. However, around half the women with this condition are asymptomatic. Diagnosis is best made by microscopic examination of a Gram-stained smear of vaginal secretions. Treatment is with metronidazole or clindamycin. The indications for treatment of asymptomatic BV are not clear, but women should probably be treated before any invasive gynaecological procedure, including intrauterine contraceptive device (IUCD) insertion. BV during pregnancy is associated with preterm labour, although a causal effect is not proven; studies are in progress to determine whether treatment of BV will improve the outcome of these pregnancies.

  19. Bacterial Actins.

    PubMed

    Izoré, Thierry; van den Ent, Fusinita

    2017-01-01

    A diverse set of protein polymers, structurally related to actin filaments contributes to the organization of bacterial cells as cytomotive or cytoskeletal filaments. This chapter describes actin homologs encoded by bacterial chromosomes. MamK filaments, unique to magnetotactic bacteria, help establishing magnetic biological compasses by interacting with magnetosomes. Magnetosomes are intracellular membrane invaginations containing biomineralized crystals of iron oxide that are positioned by MamK along the long-axis of the cell. FtsA is widespread across bacteria and it is one of the earliest components of the divisome to arrive at midcell, where it anchors the cell division machinery to the membrane. FtsA binds directly to FtsZ filaments and to the membrane through its C-terminus. FtsA shows altered domain architecture when compared to the canonical actin fold. FtsA's subdomain 1C replaces subdomain 1B of other members of the actin family and is located on the opposite side of the molecule. Nevertheless, when FtsA assembles into protofilaments, the protofilament structure is preserved, as subdomain 1C replaces subdomain IB of the following subunit in a canonical actin filament. MreB has an essential role in shape-maintenance of most rod-shaped bacteria. Unusually, MreB filaments assemble from two protofilaments in a flat and antiparallel arrangement. This non-polar architecture implies that both MreB filament ends are structurally identical. MreB filaments bind directly to membranes where they interact with both cytosolic and membrane proteins, thereby forming a key component of the elongasome. MreB filaments in cells are short and dynamic, moving around the long axis of rod-shaped cells, sensing curvature of the membrane and being implicated in peptidoglycan synthesis.

  20. Cell proliferation in carcinogenesis

    SciTech Connect

    Cohen, S.M.; Ellwein, L.B. )

    1990-08-31

    Chemicals that induce cancer at high doses in animal bioassays often fail to fit the traditional characterization of genotoxins. Many of these nongenotoxic compounds (such as sodium saccharin) have in common the property that they increase cell proliferation in the target organ. A biologically based, computerized description of carcinogenesis was used to show that the increase in cell proliferation can account for the carcinogenicity of nongenotoxic compounds. The carcinogenic dose-response relationship for genotoxic chemicals (such as 2-acetylaminofluorene) was also due in part to increased cell proliferation. Mechanistic information is required for determination of the existence of a threshold for the proliferative (and carcinogenic) response of nongenotoxic chemicals and the estimation of risk for human exposure.

  1. Sexual dysfunction with antihypertensive drugs.

    PubMed

    Prisant, L M; Carr, A A; Bottini, P B; Solursh, D S; Solursh, L P

    1994-04-11

    The relationship of antihypertensive drugs have a long history of association with sexual dysfunction; however, this relationship is poorly documented. There appears to be a higher rate of sexual dysfunction in untreated hypertensive men compared with normotensive men. Sexual dysfunction increases with age and is associated with physical and emotional symptoms. There are few studies assessing sexual dysfunction with female and African-American hypertensive patients. Sexual dysfunction is associated with impairment of quality of life and noncompliance. Since group data may hide individual drug effects, baseline data should be collected on all patients before initiating therapy with any antihypertensive agent. Although questionnaires may not provide objective information on sexual dysfunction, the response rate to direct questioning may be less than the response rate on a questionnaire and may be affected by the gender or race of the interviewer. Research protocols using a double-blind, placebo-controlled design should assess sexual dysfunction in men and women in a standardized fashion.

  2. Endothelial dysfunction in adults with obstructive sleep apnea.

    PubMed

    Lurie, Alain

    2011-01-01

    Vascular endothelial dysfunction refers to a loss of normal homeostatic functions in the blood vessels. It is characterized by reduced vasodilation and enhanced vasoconstriction functions and chronic prothrombotic and inflammatory activity. There is convincing evidence for endothelial dysfunction in obstructive sleep apnea (OSA): OSA is associated with alterations in vascular structures and their elastic properties, increased circulating cell-derived microparticles, reduced endothelial repair capacity, and vascular reactivity. These alterations may be related to the reduced availability of nitric oxide, which has major vasoprotective effects including vasodilation, inhibition of platelet adhesion and aggregation, inhibition of leukocyte-endothelial adhesion and inhibition of smooth muscle cell proliferation. It is unknown whether endothelial dysfunction in OSA is due to alterations in vasoconstriction mechanisms related to angiotensin II or endothelin 1. In OSA, endothelial dysfunction may be related to chronic intermittent hypoxia and to sleep loss and fragmentation. These conditions may increase the levels of various markers of inflammation and oxidative stress, as well as those of increased procoagulant and thrombotic activity. In addition, they may produce an imbalance of vasomotor function. Endothelial dysfunction contributes to the development of atherosclerosis and cardiovascular disorders associated with OSA. However, other diseases that are also associated with endothelial dysfunction are OSA comorbidities, e.g. obesity, insulin resistance, smoking habits and cardiovascular diseases such as hypertension and coronary artery disease. This makes it difficult to demonstrate a causal link between OSA and endothelial dysfunction; nevertheless, evidence for such a link has been produced by therapeutic studies. The administration of continuous positive airway pressure may reverse changes associated with endothelial dysfunction and, therefore, may decrease the risk

  3. Environmental enteric dysfunction: An overview

    PubMed Central

    Crane, Rosie J.; Jones, Kelsey D. J.; Berkley, James A.

    2015-01-01

    Background Environmental enteric dysfunction (EED) refers to an incompletely defined syndrome of inflammation, reduced absorptive capacity, and reduced barrier function in the small intestine. It is widespread among children and adults in low- and middle-income countries. Understanding of EED and its possible consequences for health is currently limited. Objective A narrative review of the current understanding of EED: epidemiology, pathogenesis, therapies, and relevance to child health. Methods Searches for key papers and ongoing trials were conducted using PUBMED 1966–June 2014; ClinicalTrials.gov; the WHO Clinical Trials Registry; the Cochrane Library; hand searches of the references of retrieved literature; discussions with experts; and personal experience from the field. Results EED is established during infancy and is associated with poor sanitation, certain gut infections, and micronutrient deficiencies. Helicobacter pylori infection, small intestinal bacterial overgrowth (SIBO), abnormal gut microbiota, undernutrition, and toxins may all play a role. EED is usually asymptomatic, but it is important due to its association with stunting. Diagnosis is frequently by the dual sugar absorption test, although other biomarkers are emerging. EED may partly explain the reduced efficacy of oral vaccines in low- and middle-income countries and the increased risk of serious infection seen in children with undernutrition. Conclusions Despite its potentially significant impacts, it is currently unclear exactly what causes EED and how it can be treated or prevented. Ongoing trials involve nutritional supplements, water and sanitation interventions, and immunomodulators. Further research is needed to better understand this condition, which is of likely crucial importance for child health and development in low- and middle-income settings. PMID:25902619

  4. Environmental enteric dysfunction: an overview.

    PubMed

    Crane, Rosie J; Jones, Kelsey D J; Berkley, James A

    2015-03-01

    Environmental enteric dysfunction (EED) refers to an incompletely defined syndrome of inflammation, reduced absorptive capacity, and reduced barrier function in the small intestine. It is widespread among children and adults in low- and middle-income countries. Understanding of EED and its possible consequences for health is currently limited. A narrative review of the current understanding of EED: epidemiology, pathogenesis, therapies, and relevance to child health. Searches for key papers and ongoing trials were conducted using PUBMED 1966-June 2014; ClinicalTrials.gov; the WHO Clinical Trials Registry; the Cochrane Library; hand searches of the references of retrieved literature; discussions with experts; and personal experience from the field. EED is established during infancy and is associated with poor sanitation, certain gut infections, and micronutrient deficiencies. Helicobacter pylori infection, small intestinal bacterial overgrowth (SIBO), abnormal gut microbiota, undernutrition, and toxins may all play a role. EED is usually asymptomatic, but it is important due to its association with stunting. Diagnosis is frequently by the dual sugar absorption test, although other biomarkers are emerging. EED may partly explain the reduced efficacy of oral vaccines in low- and middle-income countries and the increased risk of serious infection seen in children with undernutrition. Despite its potentially significant impacts, it is currently unclear exactly what causes EED and how it can be treated or prevented. Ongoing trials involve nutritional supplements, water and sanitation interventions, and immunomodulators. Further research is needed to better understand this condition, which is of likely crucial importance for child health and development in low- and middle-income settings.

  5. The bacterial microbiota in inflammatory lung diseases.

    PubMed

    Huffnagle, Gary B; Dickson, Robert P

    2015-08-01

    Numerous lines of evidence, ranging from recent studies back to those in the 1920s, have demonstrated that the lungs are NOT bacteria-free during health. We have recently proposed that the entire respiratory tract should be considered a single ecosystem extending from the nasal and oral cavities to the alveoli, which includes gradients and niches that modulate microbiome dispersion, retention, survival and proliferation. Bacterial exposure and colonization of the lungs during health is most likely constant and transient, respectively. Host microanatomy, cell biology and innate defenses are altered during chronic lung disease, which in turn, alters the dynamics of bacterial turnover in the lungs and can lead to longer term bacterial colonization, as well as blooms of well-recognized respiratory bacterial pathogens. A few new respiratory colonizers have been identified by culture-independent methods, such as Pseudomonas fluorescens; however, the role of these bacteria in respiratory disease remains to be determined. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. Proliferation: Threat and response

    SciTech Connect

    1996-04-01

    ;Table of Contents: Section I: The Regional Proliferation Challenge; Northeast Asia; The Middle East and North Africa; The Former Soviet Union: Russia, Ukrane, Kazakstan, And Belarus; South Asia; The International Threat: Dangers from Terrorism, Insurgencies, Civil Wars, And Organized Crime; Section II: Department of Defense Response; Technical Annex: Accessible Technologies; Glossary.

  7. JPRS Report, Proliferation Issues

    DTIC Science & Technology

    2016-03-24

    contains foreign media information on issues related to worldwide proliferation and transfer activities in nuclear , chemical, and biological weapons...Warfare [A. G. Malherbe; PARA TUS, Mar 93] . 1 Nuclear Research Training Courses To Be Held in 1994 [SAPA, 6 May 93...2 EAST ASIA REGIONAL AFFAIRS South Pacific Forum Warns France Against Restarting Nuclear Tests [AFP, 6 May 93] ................ 3 JAPAN Cooperation

  8. Bacterial vaginosis -- aftercare

    MedlinePlus

    ... page: //medlineplus.gov/ency/patientinstructions/000687.htm Bacterial vaginosis - aftercare To use the sharing features on this ... back after you use the bathroom. Preventing Bacterial Vaginosis You can help prevent bacterial vaginosis by: Not ...

  9. Pregnancy Complications: Bacterial Vaginosis

    MedlinePlus

    ... Loss > Pregnancy complications > Bacterial vaginosis and pregnancy Bacterial vaginosis and pregnancy E-mail to a friend Please ... page It's been added to your dashboard . Bacterial vaginosis (also called BV or vaginitis) is an infection ...

  10. Bacterial pericarditis (image)

    MedlinePlus

    Bacterial pericarditis is an inflammation of the pericardium, the sac-like covering of the heart, caused by a bacterial infection. The bacterial infection causes inflammation and swelling of the pericardium. Pain ...

  11. Management of ejaculatory dysfunction.

    PubMed

    McMahon, C G

    2014-02-01

    Ejaculatory dysfunction is a common complaint and is often associated with a reduced quality of life for sufferer and partner. The spectrum of ejaculatory dysfunction extends from premature ejaculation (PE) to delayed ejaculation (DE) and anejaculation. Over the past 20-30 years, the PE treatment paradigm, previously limited to behavioural psychotherapy, has expanded to include drug treatment. Multiple well-controlled, evidence-based studies have demonstrated the efficacy and safety of selective serotonin re-uptake inhibitors in delaying ejaculation, confirming their role as first-line agents for the treatment of lifelong and acquired PE. More recently, there has been increased attention to the psychosocial consequences of PE, its epidemiology, its aetiology and its pathophysiology by both clinicians and the pharmaceutical industry. DE and anejaculation are probably the least common, least studied and least understood of the male sexual dysfunctions. However, their impact is significant as they may result in a lack of sexual fulfilment for both the man and his partner, an effect further compounded when procreation is among the couple's goals of sexual intercourse. The causes of DE, anejaculation and anorgasmia are manifold. Numerous psychotherapeutic treatments are described for the management of delayed or anejaculation. Although some appear to be effective, none has been properly evaluated in large-scale samples. Treatment of DE or anejaculation with pharmacotherapy has met with limited success. No drugs have been approved by regulatory agencies for this purpose, and most drugs that have been identified for potential use have limited efficacy, impart significant side-effects or are yet considered experimental in nature.

  12. Bacterial vaginosis.

    PubMed Central

    Spiegel, C A

    1991-01-01

    Bacterial vaginosis (BV) is the most common of the vaginitides affecting women of reproductive age. It appears to be due to an alteration in the vaginal ecology by which Lactobacillus spp., the predominant organisms in the healthy vagina, are replaced by a mixed flora including Prevotella bivia, Prevotella disiens, Porphyromonas spp., Mobiluncus spp., and Peptostreptococcus spp. All of these organisms except Mobiluncus spp. are also members of the endogenous vaginal flora. While evidence from treatment trials does not support the notion that BV is sexually transmitted, recent studies have shown an increased risk associated with multiple sexual partners. It has also been suggested that the pathogenesis of BV may be similar to that of urinary tract infections, with the rectum serving as a reservoir for some BV-associated flora. The organisms associated with BV have also been recognized as agents of female upper genital tract infection, including pelvic inflammatory disease, and the syndrome BV has been associated with adverse outcome of pregnancy, including premature rupture of membranes, chorioamnionitis, and fetal loss; postpartum endometritis; cuff cellulitis; and urinary tract infections. The mechanisms by which the BV-associated flora causes the signs of BV are not well understood, but a role for H2O2-producing Lactobacillus spp. in protecting against colonization by catalase-negative anaerobic bacteria has been recognized. These and other aspects of BV are reviewed. PMID:1747864

  13. Association of peripheral microvascular dysfunction and erectile dysfunction.

    PubMed

    Gerber, Rachael E; Vita, Joseph A; Ganz, Peter; Wager, Carrie G; Araujo, Andre B; Rosen, Raymond C; Kupelian, Varant

    2015-02-01

    Increasing evidence of a link between erectile dysfunction and cardiovascular disease suggests a shared vascular etiology with endothelial dysfunction as a plausible underlying biological mechanism. To our knowledge whether this association is different for large arterial endothelium compared to microvascular endothelium has not yet been established. We investigated the association of erectile dysfunction with macrovascular and microvascular endothelial function. A sample of 390 men with a mean age of 55.5 years was recruited from the BACH survey, a population based survey of urological symptoms. Erectile dysfunction was assessed using IIEF-5. The percent of brachial artery flow mediated dilatation, a measure of macrovascular function, and hyperemic flow velocity in cm per second, a measure of microvascular function, were assessed by ultrasound. Linear regression was used to assess the association of erectile dysfunction and endothelial function, and adjust for potential confounders. Reactive hyperemia was lower in men with vs without erectile dysfunction (mean ± SE 97.1 ± 2.5 vs 106.0 ± 1.6 cm per second, p = 0.003). However, the difference in flow mediated dilatation between men with vs without erectile dysfunction was statistically nonsignificant (mean 6.6% ± 0.33% vs 7.2% ± 0.24%, p = 0.147). The association of erectile dysfunction with reactive hyperemia was attenuated but it remained statistically significant in men with moderate to severe erectile dysfunction (IIEF-5 less than 12) after adjusting for traditional cardiovascular risk factors (p = 0.038). These results provide evidence of greater microvascular than macrovascular endothelial dysfunction as a potential contributor to erectile dysfunction and an underlying mechanism linking erectile dysfunction and cardiovascular disease. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  14. Posttraumatic olfactory dysfunction.

    PubMed

    Coelho, Daniel H; Costanzo, Richard M

    2016-04-01

    Impairment of smell may occur following injury to any portion of the olfactory tract, from nasal cavity to brain. A thorough understanding of the anatomy and pathophysiology combined with comprehensively obtained history, physical exam, olfactory testing, and neuroimaging may help to identify the mechanism of dysfunction and suggest possible treatments. Although most olfactory deficits are neuronal mediated and therefore currently unable to be corrected, promising technology may provide novel treatment options for those most affected. Until that day, patient counseling with compensatory strategies and reassurance is essential for the maintenance of safety and QoL in this unique and challenging patient population.

  15. Depression and erectile dysfunction.

    PubMed

    Makhlouf, Antoine; Kparker, Ashay; Niederberger, Craig S

    2007-11-01

    Depression and erectile dysfunction (ED) clearly are associated. Although urologists and psychiatrists have long recognized that antidepressant medications affect erectile function negatively, the interplay between the two conditions remains underappreciated. Psychiatrists may be reluctant to question a patient in detail about ED, and urologists seldom perform a formal assessment of the presence of depression in patients who have ED. This article gives a quick overview of the relationship between these two conditions and provides the clinician with the knowledge required to effectively manage ED with comorbid depression.

  16. Mitochondrial dysfunction in autism.

    PubMed

    Legido, Agustín; Jethva, Reena; Goldenthal, Michael J

    2013-09-01

    Using data of the current prevalence of autism as 200:10,000 and a 1:2000 incidence of definite mitochondrial (mt) disease, if there was no linkage of autism spectrum disorder (ASD) and mt disease, it would be expected that 1 in 110 subjects with mt disease would have ASD and 1 in 2000 individuals with ASD would have mt disease. The co-occurrence of autism and mt disease is much higher than these figures, suggesting a possible pathogenetic relationship. Such hypothesis was initially suggested by the presence of biochemical markers of abnormal mt metabolic function in patients with ASD, including elevation of lactate, pyruvate, or alanine levels in blood, cerebrospinal fluid, or brain; carnitine level in plasma; and level of organic acids in urine, and by demonstrating impaired mt fatty acid β-oxidation. More recently, mtDNA genetic mutations or deletions or mutations of nuclear genes regulating mt function have been associated with ASD in patients or in neuropathologic studies on the brains of patients with autism. In addition, the presence of dysfunction of the complexes of the mt respiratory chain or electron transport chain, indicating abnormal oxidative phosphorylation, has been reported in patients with ASD and in the autopsy samples of brains. Possible pathogenetic mechanisms linking mt dysfunction and ASD include mt activation of the immune system, abnormal mt Ca(2+) handling, and mt-induced oxidative stress. Genetic and epigenetic regulation of brain development may also be disrupted by mt dysfunction, including mt-induced oxidative stress. The role of the purinergic system linking mt dysfunction and ASD is currently under investigation. In summary, there is genetic and biochemical evidence for a mitochondria (mt) role in the pathogenesis of ASD in a subset of children. To determine the prevalence and type of genetic and biochemical mt defects in ASD, there is a need for further research using the latest genetic technology such as next

  17. Dysfunctional voiding in adults.

    PubMed

    Haifler, Miki; Stav, Kobi

    2013-05-01

    Dysfunctional voiding is characterized by an intermittent and/or fluctuating flow rate due to involuntary intermittent contractions of the periurethral striated or levator muscles during voiding in neurologically normal women (International Continence Society definition). Due to the variable etiology, the diagnosis and treatment of DV is problematic. Frequently, the diagnosis is done at a late stage mainly due to non-specific symptoms and lack of awareness. The objectives of treatment are to normalize micturition patterns and prevent complications such as renal failure and recurrent infections. Treatment should be started as early as possible and a multidisciplinary approach is beneficial.

  18. [Thyroid dysfunctions and pregnancy].

    PubMed

    Caron, Philippe

    2011-12-01

    Advances in understanding the physiology of the thyroid function in normal pregnancy have highlighted the importance of the consequences of abnormal thyroid function on mother and fetal outcomes. Thyroid diseases are common in young women of childbearing age while management of thyroid diseases is relatively straightforward. For each thyroid dysfunction (hypothyroxinemia, hypothyroidism, hyperthyroidism, postpartum thyroiditis), the issues with the obstetric complications of the mother and the fetus are considered. Indeed, early recognition of thyroid diseases during pregnancy and appropriate management has the potential to improve outcome for the mother and the fetus.

  19. Small bowel bacterial overgrowth

    MedlinePlus

    Overgrowth - intestinal bacteria; Bacterial overgrowth - intestine; Small intestinal bacterial overgrowth; SIBO ... intestine does not have a high number of bacteria. Excess bacteria in the small intestine may use ...

  20. Role of Dendritic Cells in Immune Dysfunction

    NASA Technical Reports Server (NTRS)

    Savary, Cherylyn A.

    1998-01-01

    The specific aims of the project were: (1) Application of the NASA bioreactor to enhance cytokine-regulated proliferation and maturation of dendritic cells (DC). (2) Compare the frequency and function of DC in normal donors and immunocompromised cancer patients. (3) Analyze the effectiveness of cytokine therapy and DC-assisted immunotherapy (using bioreactor-expanded DC) in a murine model of experimental fungal disease. Our investigations have provided new insight into DC immunobiology and have led to the development of methodology to evaluate DC in blood of normal donors and patients. Information gained from these studies has broadened our understanding of possible mechanisms involved in the immune dysfunction of space travelers and earth-bound cancer patients, and could contribute to the design of novel therapies to restore/preserve immunity in these individuals. Several new avenues of investigation were also revealed. The results of studies completed during Round 2 are summarized.

  1. Mitochondrial Dysfunction in Obesity

    PubMed Central

    Bournat, Juan C.; Brown, Chester W.

    2016-01-01

    Purpose of the Review The review highlights recent findings regarding the functions of mitochondria in adipocytes, providing an understanding of their central roles in regulating substrate metabolism, energy expenditure, disposal of reactive oxygen species (ROS), and in the pathophysiology of obesity and insulin resistance, as well as roles in the mechanisms that affect adipogenesis and mature adipocyte function. Recent Findings Nutrient excess leads to mitochondrial dysfunction, which in turn leads to obesity-related pathologies, in part due to the harmful effects of ROS. The recent recognition of “ectopic” brown adipose in humans suggests that this tissue may play an underappreciated role in the control of energy expenditure. Transcription factors, PGC-1α and PRDM16, which regulate brown adipogenesis, and members of the TGF–β superfamily that modulate this process may be important new targets for anti-obesity drugs. Summary Mitochondria play central roles in ATP production, energy expenditure, and disposal of ROS. Excessive energy substrates lead to mitochondrial dysfunction with consequential effects on lipid and glucose metabolism. Adipocytes help to maintain the appropriate balance between energy storage and expenditure and maintaining this balance requires normal mitochondrial function. Many adipokines, including members of the TGF-beta superfamily, and transcriptional co-activators, PGC-1α and PRDM16, are important regulators of this process. PMID:20585248

  2. Managing female sexual dysfunction.

    PubMed

    Buster, John E

    2013-10-01

    Female sexual dysfunctions (FSDs) range from short-term aggravations to major emotional disturbances adversely affecting family and workplace. This review highlights diagnosis and management of the four most widely diagnosed FSDs. It initially focuses on hypoactive sexual desire disorder (HSDD) as a driving force at the heart of all other FSDs; nothing happens without sexual desire. Successful resolution of HSDD frequently facilitates resolution of other disorders. Central to understanding HSDD is the impact of aging female sexual endocrinology and its effect on both prevalence and expression patterns of FSD. Advances in this field have enabled introduction of some the most effective treatments yet described for HSDD. Sexual arousal disorder, though commonly affected by the same factors as HSDD, is heavily associated with psychotropic drugs and mood elevators. Orgasmic disorder is frequently the downstream result of other sexual dysfunctions, particularly HSDD, or the result of a major psychosexual trauma. Successful management of the underlying disorder often resolves orgasmic disorder. Sexual pain disorder is frequently the result of a gynecologic disorder, such as endometriosis, that can be substantially managed through successful treatment of that disorder. This article ends with the article's most important note: how to initiate the conversation. Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  3. Multiple organ dysfunction syndrome.

    PubMed Central

    Murray, M. J.; Coursin, D. B.

    1993-01-01

    The multiple organ dysfunction syndrome (MODS), though newly described, has manifested itself in intensive care unit (ICU) patients for several decades. As the name implies, it is a syndrome in which more than one organ system fails. Failure of these multiple organ systems may or may not be related to the initial injury or disease process for which the patient was admitted to the ICU. MODS is the leading cause of morbidity and mortality in current ICU practice. While the pathophysiology of MODS is not completely known, much evidence indicates that, during the initial injury which precipitates ICU admission, a chain of events is initiated which results in activation of several endogenous metabolic pathways. These pathways release compounds which, in and of themselves, are usually cytoprotective. However, an over exuberant activation of these endogenous systems results in an inflammatory response which can lead to development of failure in distant organs. As these organs fail, they activate and propagate the systemic inflammatory response. No therapy has proven entirely efficacious at modulating this inflammatory response and the incidence and severity of MODS. In current ICU practice, treatment is focused on prevention and treating individual organ dysfunction as it develops. With increased understanding of the pathophysiology of MODS therapy will come newer modalities which inhibit or interfere with the propagation of the endogenous systemic inflammatory response. These newer therapies hold great promise and already some are undergoing clinical investigation. PMID:7825351

  4. [Multiple organ dysfunction syndrome].

    PubMed

    Cuenca Solanas, M

    1999-01-01

    Multiple organ dysfunction syndrome (MODS) is a clinical situation that has been described as a result of the rapid progress and advances that have been made in recent decades in the physiology, diagnosis, and therapeutic support of critically ill patients. In 1991, in view of the confusing terminology used to characterize processes coursing with systemic inflammatory response syndrome (SIRS), a consensus conference was held. A series of basic definitions were established and the term "multiple organ failure" was replace by MODS. In response to outside aggression, the organism tries to defend itself with two mechanisms: a non-specific humoral and cellular response called inflammation, and a specific antigenic response that modifies the genetic codes of cells of the defense system and constitutes an immunological response. At present it is thought that the inflammatory response is activated (SIRS) in response to an uncontrolled aggression, but an antiinflammatory response syndrome (ARS) exists as well. An exaggerated SIRS can lead to MODS. MODS usually debuts with pulmonary dysfunction. If the aggression persists, cardiovascular, renal, hepatic, coagulation, central nervous system, gastrointestinal metabolism, neuroendocrine and musculoskeletal failure follow. A series of causes often trigger this syndrome and certain factors favor it. Prevention of these causes and factors in fundamental for controlling the occurrence of MODS. At present, there is no clear treatment for MODS, although numerous studies designed to block the release of certain proinflammatory mediators or to neutralize antiinflammatory responses are being carried out.

  5. Animal models of erectile dysfunction.

    PubMed

    Kapoor, Mandeep Singh; Khan, Samsroz Ahmad; Gupta, Sanjay Kumar; Choudhary, Rajesh; Bodakhe, Surendra H

    2015-01-01

    Erectile dysfunction (ED) is a prevalent male sexual dysfunction with profound adverse effects on the physical and the psychosocial health of men and, subsequently, on their partners. The expanded use of various types of rodent models has produced some advances in the study of ED, and neurophysiological studies using various animal models have provided important insights into human sexual dysfunction. At present, animal models play a key role in exploring and screening novel drugs designed to treat ED.

  6. Quantitative bacterial flora of acute appendicitis.

    PubMed Central

    Roberts, J P

    1988-01-01

    A quantitative bacteriological study of the appendix wall of 43 children admitted to this unit showed no significant differences between the flora of the histologically normal and acutely inflamed appendices. Bacteroides species, Escherichia coli, and streptococcal species were the commonest organisms isolated and were found in counts of 10(3) to 10(8) organisms per gram of tissue. Bacteroides species were most commonly the dominant flora in both normal and inflamed appendices. The lack of increased counts of organisms in acute inflammation of the appendix suggests an unfavourable environment to bacterial proliferation making primary bacterial infection an unlikely aetiological factor in the pathogenesis of appendicitis. PMID:3389871

  7. Autonomic dysfunction in multiple sclerosis.

    PubMed

    Racosta, Juan Manuel; Kimpinski, Kurt; Morrow, Sarah Anne; Kremenchutzky, Marcelo

    2015-12-01

    Autonomic dysfunction is a prevalent and significant cause of disability among patients with multiple sclerosis. Autonomic dysfunction in multiple sclerosis is usually explained by lesions within central nervous system regions responsible for autonomic regulation, but novel evidence suggests that other factors may be involved as well. Additionally, the interactions between the autonomic nervous system and the immune system have generated increased interest about the role of autonomic dysfunction in the pathogenesis of multiple sclerosis. In this paper we analyze systematically the most relevant signs and symptoms of autonomic dysfunction in MS, considering separately their potential causes and implications.

  8. Motility, Survival and Proliferation

    PubMed Central

    Gerthoffer, William T.; Schaafsma, Dedmer; Sharma, Pawan; Ghavami, Saeid; Halayko, Andrew J

    2014-01-01

    Airway smooth muscle has classically been of interest for its contractile response linked to bronchoconstriction. However, terminally differentiated smooth muscle cells are phenotypically plastic and have multifunctional capacity for proliferation, cellular hypertrophy, migration, and the synthesis of extracellular matrix and inflammatory mediators. These latter properties of airway smooth muscle are important in airway remodeling which is a structural alteration that compounds the impact of contractile responses on limiting airway conductance. In this overview we describe the important signaling components and the functional evidence supporting a view of smooth muscle cells at the core of fibroproliferative remodeling of hollow organs. Signal transduction components and events are summarized that control the basic cellular processes of proliferation, cell survival, apoptosis and cellular migration. We delineate known intracellular control mechanisms and suggest future areas of interest to pursue to more fully understand factors that regulate normal myocyte function and airway remodeling in obstructive lung diseases. PMID:23728975

  9. JPRS Report, Proliferation Issues

    DTIC Science & Technology

    2016-03-24

    place, either North Korea will move positively pendence as their life and soul and that they will only face on solving the nuclear stalemate or Beijing...test chamber, a 15-meter steel cube in which test animals are subjected to a fine spray from vents in the ceiling. This [Corresponent] But there is no...information on issues related to worldwide proliferation and transfer activities in nuclear, chemical, and biological weapons, including delivery systems and

  10. JPRS Report: Proliferation Issues

    DTIC Science & Technology

    2016-03-24

    nuclear -related infor- Korea imports uranium from the United States and mation with Japan for the purpose of checking Japan’s Canada for its reactors and...foreign media information on issues related to worldwide proliferation and transfer activities in nuclear , chemical, and biological weapons, including...I Antinuclear Group Alleges ’ Nuclear Link’ With Japan [WEEKEND ARGUS 7 Nov] ................ 2 Chemical Weapons Convention Signing

  11. Proliferating pilomatricoma - Case report*

    PubMed Central

    Kondo, Rogerio Nabor; Pontello Junior, Rubens; Belinetti, Francine Milenkovich; Cilião, Caroline; Vasconcellos, Vanessa Regina Bulla; Grimaldi, Dora Maria

    2015-01-01

    Proliferating pilomatricoma is proliferative, rare tumor variant of pilomatricoma. It is a benign neoplasm of hair matrix that can have potentially involve local recurrence. We report the case of a 60-year-old man who presented an asymptomatic nodule on the scalp. Histological exam demonstrated a basaloid epithelium at the periphery, filled with eosinophilic cornified material containing shadow cells. The tumor was excised and there was no evidence of recurrence one year later. PMID:26312685

  12. JPRS report proliferation issues

    SciTech Connect

    1991-11-07

    This report contains foreign media information on issues related to worldwide proliferation and transfer activities in nuclear, chemical, and biological weapons, including delivery systems and the transfer of weapons relevant technologies. The following locations are included: (1) South Africa; (2) China; (3) North and South Korea, Japan; (4) Bulgaria, Czechoslovakia; (5) Argentina, Brazil; (6) India, Iran, Israel, Pakistan, Libya, Iraq, Egypt; (7) Soviet Union; and (8) Belgium, Germany, United Kingdom, Netherlands, France.

  13. JPRS report proliferation issues

    SciTech Connect

    1991-09-27

    This report contains foreign media information on issues related to worldwide proliferation and transfer activities in nuclear, chemical, and biological weapons, including delivery systems and the transfer of weapons relevant technologies. The following locations are included: (1) South Africa, Namibia; (2) China; (3) South Korea, Australia, Indonesia, Japan, Philippines; (4) Yugoslavia; (5) Brazil, Argentina, Cuba; (6) India, Libya, Pakistan; (7) Soviet Union; and (8) France, Germany, Netherlands.

  14. Electronic mail dysfunction: a reality check.

    PubMed

    Case, C J

    1999-01-01

    Computer-mediated communication systems, including electronic mail, are systems that businesses employ to improve efficiency, effectiveness, and communication within the organization. As use of these systems proliferate, it is crucial that the communication systems have a positive, rather than negative impact, on the organization. Negative behavior could include flaming and personal use of the electronic mail system. Much of prior research has examined the use of electronic mail in academic settings. Results indicate that flaming and personal use have a relative high incidence. However, is electronic mail dysfunction a consistent reality for both academia and the business world? This case study empirically examines the role of electronic messaging in business firms. Specifically, this research investigates the usage of inter-organizational electronic messaging in intermediate-size firms. Electronic mail messages were analyzed in a three-site case study. Results indicate that dysfunctional electronic mail uses such as personal use and flaming have minimal incidence in a business environment. Implications relate to organizational professionalism and the use of students as electronic mail research subjects.

  15. Bacterial phospholipases.

    PubMed

    Titball, R W

    1998-01-01

    context it is worth bearing in mind that eukaryotic phospholipases C, which play key roles in many inflammatory and autoimmune diseases, are the subject of intense study by the pharmaceutical industry. Some of the bacterial toxins are potent cytotoxic agents and this has encouraged some workers to explore the possibility that immunotoxins can be developed (Chovnick et al. 1991). Purified recombinant phospholipases C will continue to be used in the study of cell membranes, and the increasing numbers of enzymes with different substrate specificities will enhance their application.

  16. Proliferation: Threat and Response

    DTIC Science & Technology

    2001-01-01

    inflamed, the animal invariable becomes lame. Livestock raised for meat lose much weight, and dairy cattle and goats give far less milk . FMD usually...be used for treatment following a biological attack with bacterial agent. The biological warfare threat of anthrax presents a potential danger to U.S...fanatical terrorists or self-proclaimed apocalyptic prophets. The followers of Usama bin Laden have, in fact, already trained with toxic chemicals

  17. Telomere dysfunction and chromothripsis.

    PubMed

    Ernst, Aurélie; Jones, David T W; Maass, Kendra K; Rode, Agata; Deeg, Katharina I; Jebaraj, Billy Michael Chelliah; Korshunov, Andrey; Hovestadt, Volker; Tainsky, Michael A; Pajtler, Kristian W; Bender, Sebastian; Brabetz, Sebastian; Gröbner, Susanne; Kool, Marcel; Devens, Frauke; Edelmann, Jennifer; Zhang, Cindy; Castelo-Branco, Pedro; Tabori, Uri; Malkin, David; Rippe, Karsten; Stilgenbauer, Stephan; Pfister, Stefan M; Zapatka, Marc; Lichter, Peter

    2016-06-15

    Chromothripsis is a recently discovered form of genomic instability, characterized by tens to hundreds of clustered DNA rearrangements resulting from a single dramatic event. Telomere dysfunction has been suggested to play a role in the initiation of this phenomenon, which occurs in a large number of tumor entities. Here, we show that telomere attrition can indeed lead to catastrophic genomic events, and that telomere patterns differ between cells analyzed before and after such genomic catastrophes. Telomere length and telomere stabilization mechanisms diverge between samples with and without chromothripsis in a given tumor subtype. Longitudinal analyses of the evolution of chromothriptic patterns identify either stable patterns between matched primary and relapsed tumors, or loss of the chromothriptic clone in the relapsed specimen. The absence of additional chromothriptic events occurring between the initial tumor and the relapsed tumor sample points to telomere stabilization after the initial chromothriptic event which prevents further shattering of the genome.

  18. Endocrine dysfunction in leprosy.

    PubMed

    Leal, A M O; Foss, N T

    2009-01-01

    Leprosy is still an endemic disease, especially in Third World countries, and, because of migration, it still persists in Europe and the United States. The disease affects the peripheral nerves, skin, and multiple internal organs, making its clinical recognition difficult. In particular, the endocrine manifestations caused by leprosy have been underestimated, even by specialists. The endocrine changes present in leprosy include hypogonadism, sterility, and osteoporosis. In addition, the spectral immune nature of leprosy offers an attractive model to investigate the pathogenetic correlation between the patterns of inflammation in the poles of its spectrum and the hormonal disarrangements observed in this disease. It is important that those involved in leprosy management be aware of the potential endocrine changes and their treatment to address the disease in all of its aspects. In this article, we review the findings on endocrine dysfunction in leprosy, including a survey of the literature and of our own work.

  19. Investigation of erectile dysfunction.

    PubMed

    Patel, D V; Halls, J; Patel, U

    2012-11-01

    Erectile dysfunction (ED) represents a common and debilitating condition with a wide range of organic and non-organic causes. Physical aetiologies can be divided into disorders affecting arterial inflow, the venous occlusion mechanism or the penile structure itself. Various imaging modalities can be utilised to investigate the physical causes of ED, but penile Doppler sonography (PDS) is the most informative technique, indicated in those patients with ED who do not respond to oral pharmacological agents (e.g. phosphodiesterase type 5 inhibitors). This review will examine the anatomical and physiological basis of penile erection, the method for performing PDS and features of specific causes of ED, and will also consider the alternative imaging modalities available.

  20. Psychotropics and sexual dysfunction

    PubMed Central

    Bella, Anthony J.

    2013-01-01

    Introduction Sexual dysfunction (SD) is common in patients taking antipsychotics, and is the most bothersome symptom and adverse drug effect compromising treatment compliance. Mechanisms involved in psychotropics–induced SD are either largely unknown or poorly understood. The aim of this review is to present an updated analysis of SD associated with the use of psychotropic drugs in psychiatric patients. Results Contemporary evidence from available studies demonstrates that SD rates are drug–related rather than drug–class specific, and that these rates vary widely. Mechanisms involved in psychotropics–induced SD are either largely unknown or poorly understood. Our understanding of psychotropics–induced SD is limited by the inability to differentiate whether these effects are really drug–induced or due to different inclusion criteria. Conclusions Rigorous research, basic and clinical, is needed to understand the exact incidence, severity and mechanisms involved in the development of SD induced by various psychotropic treatment regimens. PMID:24757547

  1. Environmental Enteric Dysfunction and the Fecal Microbiota in Malawian Children.

    PubMed

    Ordiz, M Isabel; Stephenson, Kevin; Agapova, Sophia; Wylie, Kristine M; Maleta, Ken; Martin, John; Trehan, Indi; Tarr, Phillip I; Manary, Mark J

    2017-02-08

    Environmental enteric dysfunction (EED) is often measured with a dual sugar absorption test and implicated as a causative factor in childhood stunting. Disturbances in the gut microbiota are hypothesized to be a mechanism by which EED is exacerbated, although this supposition lacks support. We performed 16S ribosomal RNA gene sequencing of fecal samples from 81 rural Malawian children with varying degrees of EED to determine which bacterial taxa were associated with EED. At the phyla level, Proteobacteria abundance is reduced with severe EED. Among bacterial genera, Megasphaera, Mitsuokella, and Sutterella were higher in EED and Succinivibrio, Klebsiella, and Clostridium_XI were lower in EED. Bacterial diversity did not vary with the extent of EED. Though EED is a condition that is typically believed to affect the proximal small bowel, and our focus was on stool, our data do suggest that there are intraluminal microbial differences that reflect, or plausibly lead to, EED.

  2. Antihypertensive therapy causes erectile dysfunction.

    PubMed

    Chrysant, Steven G

    2015-07-01

    Erectile dysfunction is a common sexual disorder affecting 40% of men in the United States. However, the pathophysiologic mechanism involved in the causation of erectile dysfunction is multifactorial and not well delineated. Several recent studies disclose that erectile dysfunction is the result of multiple interrelated comorbid conditions that include hypertension, coronary artery disease (CAD), heart failure, and diabetes mellitus among them. In addition to comorbid conditions, certain cardiovascular and antihypertensive drugs are also involved in the development of erectile dysfunction, with the most prominent being the thiazide type diuretics, the aldosterone receptor blockers, and the β-adrenergic receptor blockers. Also, knowledge by the patient of the drug and its action on erectile dysfunction may increase the incidence of erectile dysfunction (Hawthorn effect). Before treatment is initiated, patients should be screened for the presence of erectile dysfunction, because this condition is associated with hypertension, CAD, heart failure, diabetes mellitus, and their treatment and an appropriate treatment regimen should be selected. If that fails, the addition of phosphodiesterase 5 inhibitors to the treatment regimen is recommended. The only exception is a patient with CAD treated with organic nitrates, in which the coadministration of phosphodiesterase 5 inhibitors is strictly prohibited. Knowledge of the various comorbid conditions and their treatment associated with the development of erectile dysfunction will help the caring physician to treat his patients appropriately and safely. All these aspects will be discussed in this review.

  3. Diaphragmatic dysfunction in mechanical ventilation.

    PubMed

    Haitsma, Jack J

    2011-04-01

    It has become clear from experimental data that prolonged mechanical ventilation can induce diaphragm dysfunction, also known as ventilator-induced diaphragm dysfunction. In this article we will discuss most recent understanding on ventilator-induced diaphragm dysfunction and data on diaphragm dysfunction in patients. Over the last year several studies confirmed the existence of diaphragm dysfunction in patients. Known atrophy pathways are activated in patients undergoing prolonged conventional ventilation resulting in muscle proteolysis and a decrease in myofiber content. The loss of diaphragm force is time-dependent, but current data do not distinguish between the role played by other factors involved in diaphragm dysfunction. Diaphragm dysfunction occurs in patients, especially when ventilated with controlled modes of ventilation that minimize diaphragm activity. Time on the ventilator seems to be one of the biggest risk factors resulting in difficulties in weaning patients and prolonging time on the ventilator. Future trials should investigate whether improved patient-ventilator synchrony can reduce ventilator-induced diaphragm dysfunction and decrease weaning failure.

  4. [Sexual dysfunction in torture victims].

    PubMed

    Theilade, Lotte D Arlø

    2002-10-07

    Sexual dysfunction is seen in up to 51% of torture victims. The torture victim seldom reports anything about having been tortured but often consults the health care system because of a somatic problem which may seem unrelated to torture. Therefore, it is important that doctors are aware of the possible correlation. Symptoms and findings may be both physical and psychical. The torture may be both sexual and non-sexual as well as physical and non-physical. Social, cultural and individual factors also influence the development of sexual dysfunction in a torture victim. The factors that cause sexual dysfunction and the identification of any direct causal relations are discussed. There are indications that sexual torture has a greater impact on the development of sexual dysfunction than other types of torture and it seems that sexual dysfunction is a result of many factors.

  5. Respiratory dysfunction in Parkinson's disease.

    PubMed

    Forsyth, D; Torsney, K M

    2017-03-01

    Respiratory dysfunction has been associated with Parkinson's disease since it was first described in 1817. The respiratory symptoms observed in Parkinson's disease patients vary greatly. Most patients remain asymptomatic, whereas others present with acute shortness of breath and even stridor. In August 2016, an electronic literature search was conducted using PubMed and Google Scholar. Results were screened and studies reporting on respiratory dysfunction associated with Parkinson's disease were included. Respiratory dysfunction is due to a combination of factors including restrictive changes, upper airway obstruction, abnormal ventilatory drive and response to medications. Much debate surrounds the mechanism underlying respiratory dysfunction in Parkinson's disease, its prevalence and the effect of levodopa on respiration. It is clear from this review that larger studies, comparing patients of similar disease duration and severity using the same pulmonary function parameters, are required to provide a better understanding of the pathophysiology underlying respiratory dysfunction in Parkinson's disease.

  6. A burning issue: do sepsis and systemic inflammatory response syndrome (SIRS) directly contribute to cardiac dysfunction?

    PubMed

    Ren, Jun; Wu, Shan

    2006-01-01

    Heart disease is among the leading causes of death in all populations. Cardiac dysfunctions are major complications in patients with advanced viral or bacterial infection, severe trauma and burns accompanied with multiple organ failure - collectively known as systemic inflammatory response syndrome (SIRS). SIRS, which is often subsequent to sepsis, is clinically featured by hypotension, tachypnea, hypo- or hyperthermia, leukocytosis and myocardial dysfunction. The striking association between inflammation and cardiac dysfunction not only prognoses likelihood of survival in patients with SIRS but also prompts the necessity of understanding the pathophysiology of cardiac dysfunction in SIRS, so that effective therapeutic regimen may be identified. Compelling evidence has shown significant and independent link among inflammation, sepsis, insulin resistance and cardiac dysfunction. Several cytokine signaling molecules have been speculated to play important roles in the onset of cardiac dysfunction under SIRS including endothelin-1 and toll-like receptor. Involvement of these pathways in cardiac dysfunction has been convincingly validated with transgenic studies. Nevertheless, the precise mechanism of action underscoring inflammation-induced cardiac contractile dysfunction is far from being clear. Given the substantial impact of inflammation and SIRS on health care, ecosystems and national economy, it is imperative to understand the cellular mechanisms responsible for cardiac contractile dysfunction under inflammation and sepsis so that new and effective therapeutic strategy against such devastating heart problems may be developed.

  7. Erectile dysfunction in psoriasis patients.

    PubMed

    Cabete, Joana; Torres, Tiago; Vilarinho, Tiago; Ferreira, Ana; Selores, Manuela

    2014-01-01

    An association between psoriasis and sexual dysfunction has been explored. However, not much is known about the factors behind erectile dysfunction in these patients. To compare the prevalence and the severity of erectile dysfunction in patients with and without psoriasis and to determine potential associations between erectile dysfunction and psoriasis patients' characteristics. An observational cross-sectional study was conducted at two tertiary hospital-based Dermatology departments. Consecutive adult men with psoriasis or other skin conditions were recruited. Data were collected using an anonymous, self-completed, designed questionnaire, which included the Dermatology Life Quality Index and the 5-item version of the International Index of Erectile Function. A total of 135 psoriasis patients and 201 controls were included. Psoriasis patients had a higher prevalence of erectile dysfunction than controls (61.5% vs 43.8%, p = 0.001), and an increased risk of more severe forms of erectile dysfunction. Dermatology Life Quality Index, genital psoriasis and psoriasis duration were not associated with the presence of erectile dysfunction. In multivariate logistic regression, psoriasis and diabetes were found to be independent risk factors for erectile dysfunction with estimated odds ratios of 2.28 (CI 95%, 1.40-3.27) and 3.49 (CI 95%, 1.40-8.66), respectively. This study suggests psoriasis as a risk factor for erectile dysfunction. Atherosclerosis is a plausible connecting link, adding up to the already acknowledged effect of psychological factors in these patients. From a clinical standpoint, because erectile dysfunction may precede overt cardiovascular disease, it can be used as a precocious marker of cardiovascular risk in psoriatic men.

  8. Aerobic glycolysis: beyond proliferation.

    PubMed

    Jones, William; Bianchi, Katiuscia

    2015-01-01

    Aerobic glycolysis has been generally associated with cancer cell proliferation, but fascinating and novel data show that it is also coupled to a series of further cellular functions. In this Mini Review, we will discuss some recent findings to illustrate newly defined roles for this process, in particular in non-malignant cells, supporting the idea that metabolism can be considered as an integral part of cellular signaling. Consequently, metabolism should be regarded as a plastic and highly dynamic determinant of a wide range of cellular specific functions.

  9. Blockade of Urotensin II Receptor Prevents Vascular Dysfunction

    PubMed Central

    Kim, Young-Ae; Lee, Dong Gil; Yi, Kyu Yang; Lee, Byung Ho; Jung, Yi-Sook

    2016-01-01

    Urotensin II (UII) is a potent vasoactive peptide and mitogenic agent to induce proliferation of various cells including vascular smooth muscle cells (VSMCs). In this study, we examined the effects of a novel UII receptor (UT) antagonist, KR-36676, on vasoconstriction of aorta and proliferation of aortic SMCs. In rat aorta, UII-induced vasoconstriction was significantly inhibited by KR-36676 in a concentration-dependent manner. In primary human aortic SMCs (hAoSMCs), UII-induced cell proliferation was significantly inhibited by KR-36676 in a concentration-dependent manner. In addition, KR-36676 decreased UII-induced phosphorylation of ERK, and UII-induced cell proliferation was also significantly inhibited by a known ERK inhibitor U0126. In mouse carotid ligation model, intimal thickening of carotid artery was dramatically suppressed by oral treatment with KR-36676 (30 mg/ kg/day) for 4 weeks compared to vehicle-treated group. From these results, it is indicated that KR-36676 suppress UII-induced proliferation of VSMCs at least partially through inhibition of ERK activation, and that it also attenuates UII-induced vasoconstriction and vascular neointima formation. Our study suggest that KR-36676 may be an attractive candidate for the pharmacological management of vascular dysfunction. PMID:27582556

  10. Initiatives for proliferation prevention

    SciTech Connect

    1997-04-01

    Preventing the proliferation of weapons of mass destruction is a central part of US national security policy. A principal instrument of the Department of Energy`s (DOE`s) program for securing weapons of mass destruction technology and expertise and removing incentives for scientists, engineers and technicians in the newly independent states (NIS) of the former Soviet Union to go to rogue countries or assist terrorist groups is the Initiatives for Proliferation Prevention (IPP). IPP was initiated pursuant to the 1994 Foreign Operations Appropriations Act. IPP is a nonproliferation program with a commercialization strategy. IPP seeks to enhance US national security and to achieve nonproliferation objectives by engaging scientists, engineers and technicians from former NIS weapons institutes; redirecting their activities in cooperatively-developed, commercially viable non-weapons related projects. These projects lead to commercial and economic benefits for both the NIS and the US IPP projects are funded in Russian, Ukraine, Kazakhstan and Belarus. This booklet offers an overview of the IPP program as well as a sampling of some of the projects which are currently underway.

  11. Peroxisome proliferator-activated receptor {alpha}-independent peroxisome proliferation

    SciTech Connect

    Zhang Xiuguo; Tanaka, Naoki . E-mail: naopi@hsp.md.shinshu-u.ac.jp; Nakajima, Takero; Kamijo, Yuji; Gonzalez, Frank J.; Aoyama, Toshifumi

    2006-08-11

    Hepatic peroxisome proliferation, increases in the numerical and volume density of peroxisomes, is believed to be closely related to peroxisome proliferator-activated receptor {alpha} (PPAR{alpha}) activation; however, it remains unknown whether peroxisome proliferation depends absolutely on this activation. To verify occurrence of PPAR{alpha}-independent peroxisome proliferation, fenofibrate treatment was used, which was expected to significantly enhance PPAR{alpha} dependence in the assay system. Surprisingly, a novel type of PPAR{alpha}-independent peroxisome proliferation and enlargement was uncovered in PPAR{alpha}-null mice. The increased expression of dynamin-like protein 1, but not peroxisome biogenesis factor 11{alpha}, might be associated with the PPAR{alpha}-independent peroxisome proliferation at least in part.

  12. Disease, dysfunction, and synthetic biology.

    PubMed

    Holm, Sune

    2014-08-01

    Theorists analyzing the concept of disease on the basis of the notion of dysfunction consider disease to be dysfunction requiring. More specifically, dysfunction-requiring theories of disease claim that for an individual to be diseased certain biological facts about it must be the case. Disease is not wholly a matter of evaluative attitudes. In this paper, I consider the dysfunction-requiring component of Wakefield's hybrid account of disease in light of the artifactual organisms envisioned by current research in synthetic biology. In particular, I argue that the possibility of artifactual organisms and the case of oncomice and other bred or genetically modified strains of organism constitute a significant objection to Wakefield's etiological account of the dysfunction requirement. I then develop a new alternative understanding of the dysfunction requirement that builds on the organizational theory of function. I conclude that my suggestion is superior to Wakefield's theory because it (a) can accommodate both artifactual and naturally evolved organisms, (b) avoids the possibility of there being a conflict between what an organismic part is supposed to do and the health of the organism, and (c) provides a nonarbitrary and practical way of determining whether dysfunction occurs.

  13. Understanding brain dysfunction in sepsis

    PubMed Central

    2013-01-01

    Sepsis often is characterized by an acute brain dysfunction, which is associated with increased morbidity and mortality. Its pathophysiology is highly complex, resulting from both inflammatory and noninflammatory processes, which may induce significant alterations in vulnerable areas of the brain. Important mechanisms include excessive microglial activation, impaired cerebral perfusion, blood–brain-barrier dysfunction, and altered neurotransmission. Systemic insults, such as prolonged inflammation, severe hypoxemia, and persistent hyperglycemia also may contribute to aggravate sepsis-induced brain dysfunction or injury. The diagnosis of brain dysfunction in sepsis relies essentially on neurological examination and neurological tests, such as EEG and neuroimaging. A brain MRI should be considered in case of persistent brain dysfunction after control of sepsis and exclusion of major confounding factors. Recent MRI studies suggest that septic shock can be associated with acute cerebrovascular lesions and white matter abnormalities. Currently, the management of brain dysfunction mainly consists of control of sepsis and prevention of all aggravating factors, including metabolic disturbances, drug overdoses, anticholinergic medications, withdrawal syndromes, and Wernicke’s encephalopathy. Modulation of microglial activation, prevention of blood–brain-barrier alterations, and use of antioxidants represent relevant therapeutic targets that may impact significantly on neurologic outcomes. In the future, investigations in patients with sepsis should be undertaken to reduce the duration of brain dysfunction and to study the impact of this reduction on important health outcomes, including functional and cognitive status in survivors. PMID:23718252

  14. [Thyroid dysfunction during pregnancy].

    PubMed

    Díez, Juan J; Iglesias, Pedro; Donnay, Sergio

    2015-10-21

    Recent clinical practice guidelines on thyroid dysfunction and pregnancy have changed health care provided to pregnant women, although their recommendations are under constant revision. Trimester- and area-specific reference ranges for serum thyroid-stimulating hormone are required for proper diagnosis of hypothyroidism and hyperthyroidism. There is no doubt on the need of therapy for overt hypothyroidism, while therapy for subclinical hypothyroidism is controversial. Further research is needed to settle adverse effects of isolated hypothyroxinemia and thyroid autoimmunity. Differentiation between hyperthyroidism due to Graves' disease and the usually self-limited gestational transient thyrotoxicosis is critical. It is also important to recognize risk factors for postpartum thyroiditis. Supplementation with iodine is recommended to maintain adequate iodine nutrition during pregnancy and avoid serious consequences in offspring. Controversy remains about universal screening for thyroid disease during pregnancy or case-finding in high-risk women. Opinions of some scientific societies and recent cost-benefit studies favour universal screening. Randomized controlled studies currently under development should reduce the uncertainties that still remain in this area. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

  15. Psychoanalysis: a dysfunctional family?

    PubMed

    Grosskurth, P

    1998-01-01

    The discussion opens with an account of the author's mother's bizarre family in which a strong, charismatic grandmother maintained absolute control over her large family by encouraging a neurotic dependence in them through daily reports of their complaints. Getting interested in psychoanalysis in an effort to understand the dynamics of this dysfunctional family, the author, a biographer, turned to the study of Melanie Klein, becoming entranced by her ideas. Her research also revealed how Klein had discouraged her followers from developing ideas that diverged in any way from her own. Her portrait of the pioneer analyst provoked intense indignation. A similar pattern of absolute loyalty to his person and theories was to be found in Freud's Secret Committee, formed primarily as a means of getting rid of Jung who had been showing disturbing signs of independence. When Ferenczi and Rank began to pursue independent lines of enquiry in their work, they too were though to be undermining the foundations of classical psychoanalysis. Finally, the author concludes that though there have been sorry incidents in psychoanalysis, we should be mature enough to accept both the contributions of the early pioneers and the realizations that new ideas must be permitted to evolve.

  16. Multiple organ dysfunction syndrome.

    PubMed

    Ramírez, Michelle

    2013-01-01

    Initially known as multiple system organ failure, the term multiple organ dysfunction syndrome (MODS) was first described in the 1960s in adults with bleeding, respiratory failure, and sepsis. It is defined as "the development of potentially reversible physiologic derangement involving two or more organ systems not involved in the disorder that resulted in ICU admission, and arising in the wake of a potentially life threatening physiologic insult."(3) There are many risk factors predisposing to MODS; however, the most common risk factors are shock due to any cause, sepsis, and tissue hypoperfusion. A dysregulated immune response, or immuneparalysis, in which the homeostasis between pro-inflammatory and anti-inflammatory reaction is lost is thought to be key in the development of MODS. The clinical course and evolution of MODS is dependent on a combination of acquired and genetic factors. There are several nonspecific therapies for the prevention and resolution of MODS, mostly care is supportive. Mortality from MODS in septic pediatric patients varies between 11% and 54%. © 2013 Published by Mosby, Inc.

  17. [Female sexual dysfunction].

    PubMed

    Luria, Mijal

    2009-09-01

    Female sexual problems are common, frequently overlooked and have a significant impact on the lives of women. Research in the last decade has brought to the understanding and recognition of a number of standpoints, mainly the broad range of normative function. In 2003, the American Urological Association Foundation convened an international committee of experts in the field of women's sexuality, to reconsider the existing definitions of women's sexual dysfunction. Based on the circular response cycle developed by Basson, the group emphasized motivations that might move a woman from being sexually "neutral" to making a decision to be sexual with her partner, as a normative alternative to the need for spontaneous sexual desire as the trigger for sexual behavior. Etiology may stem from medical as well as psychological factors, thus assessment must include a complete evaluation. Treatment includes psycho-education, improvement of interpersonal communication, cognitive behavioral treatment and elucidation and treatment of medical problems, if necessary. Several pharmacological treatments are under investigation, with modest results and uncertainties about their long term safety. This review presents the female sexual response as it is understood today and the current diagnostic and therapeutic understandings and directions.

  18. Markers of erectile dysfunction

    PubMed Central

    Davies, Kelvin P.; Melman, Arnold

    2008-01-01

    With the development and marketing of oral pharmacotherapy that is both noninvasive and successful in treating erectile dysfunction (ED), the quest to identify markers of organic ED lost ground. Indeed, the multi-factorial nature of ED may have led many researchers to conclude that searching for a universal marker of ED was futile. However, the realization that ED is strongly correlated with the overall health of men, and may act as a predictor for the development of cardiovascular disease (CVD) and diabetes, has stimulated interest in identifying genes that can distinguish organic ED. In addition, the potential ability to suggest to the patient that ED is reversible (i.e., psychogenic) with a simple test would be of significance to both the physician and patient, as well as for reimbursement issues for therapy by insurance companies. Such a marker may also act as a non-subjective measure of the degree of ED and the efficacy of treatment. This review discusses the importance of identifying such markers and recent work identifying potential markers in human patients. PMID:19468461

  19. [Hypothalamic dysfunction in obesity].

    PubMed

    van de Sande-Lee, Simone; Velloso, Licio A

    2012-08-01

    Obesity, defined as abnormal or excessive fat accumulation that may impair life quality, is one of the major public health problems worldwide. It results from an imbalance between food intake and energy expenditure. The control of energy balance in animals and humans is performed by the central nervous system (CNS) by means of neuroendocrine connections, in which circulating peripheral hormones, such as leptin and insulin, provide signals to specialized neurons of the hypothalamus reflecting body fat stores, and induce appropriate responses to maintain the stability of these stores. The majority of obesity cases are associated with central resistance to both leptin and insulin actions. In experimental animals, high-fat diets can induce an inflammatory process in the hypothalamus, which impairs leptin and insulin intracellular signaling pathways, and results in hyperphagia, decreased energy expenditure and, ultimately, obesity. Recent evidence obtained from neuroimaging studies and assessment of inflammatory markers in the cerebrospinal fluid of obese subjects suggests that similar alterations may be also present in humans. In this review, we briefly present the mechanisms involved with the loss of homeostatic control of energy balance in animal models of obesity, and the current evidence of hypothalamic dysfunction in obese humans.

  20. [Characteristics of postpartum thyroid dysfunction].

    PubMed

    Argatska, A; Nonchev, B; Obretsova, M; Pehlivanov, B

    2015-01-01

    The risk factors and mechanisms for the development of postpartum thyroid dysfunction have been widely discussed. However data on patients suffered spontaneous or induced abortion during early pregnancy are scarce. To reveal the characteristics of thyroid dysfunction in women after an abortion in the first trimester of pregnancy. A total of 28 women (18 euthyroid, 10 with thyroid dysfunction), mean age 30.46 ± 1.01 years following abortion in the first trimester have been included in the study. Thyroid-stimulating hormone (TSH), free triiodthyronine (FT3), free thyroxine (FT4), thyreoglobulin antibodies (TgAb), thyroid peroxidase antibodies (TPOAb) were measured and ultrasound assessment of the thyroid was performed 3 and 9 months after the interruption of pregnancy. Hypothyroidism was found in 6 of the women with thyroid dysfunction and thyrotoxicosis--in 4. Clinical features of thyroid dysfunction were observed in 3 patients while in the remaining 7 cases, diagnosis was made on the basis of hormonal levels. Positive titers of thyroid autoantibodies were detected in the majority of the cases with functional disordes. In 6 patients thyroid dysfunction was transient and in 4 hormonal abnormalities persisted on by the 9th month after the abortion. The comparative analysis showed that the volume of the thyroid gland and the degree of hypoehogenicity were significantly higher in patients with thyroid dysfunction compared to euthyroid women. Thyroid dysfunction after abortion in the first trimester is mainly of autoimmune pathogenesis and its characteristics do not differ from those of postpartum thyroiditis. In the majority of patients these disorders are subclinical and may remain unrecognized. A close active follow up of patients at increased risk of functional thyroid disorders after an abortion is required in order to prevent morbidity and identify the cases developing permanent thyroid dysfunction.

  1. Strapping for temporomandibular joint dysfunction.

    PubMed

    Babu, Abraham Samuel; John, Sandhya Mary; Unni, Amith

    2008-01-01

    Temporomandibular joint dysfunction (TMJD) is a common problem seen in many of the dental clinics. Management of this depends on an accurate diagnosis of the cause for the TMJD. Physical therapy and rehabilitation play a vital role in the management of these dysfunctions. Physical therapy is useful in treating post-traumatic stiffness of the TMJ while strapping of the TMJ for a dysfunction along with conventional physical therapy is of benefit in terms of reduction in click, decrease in pain, and an improvement in function.

  2. Sacroiliac joint dysfunction in athletes.

    PubMed

    Brolinson, P Gunnar; Kozar, Albert J; Cibor, Greg

    2003-02-01

    The sacroiliac (SI) joint is a common source of low back pain in the general population. Because it is the link between the lower extremities and the spine, it sustains even higher loads during athletic activity, predisposing athletes to a greater probability of joint dysfunction and pain. The diagnosis and treatment of SI joint dysfunction remains controversial, due to complex anatomy and biomechanics, and a lack of universally accepted nomenclature and terminology, consistently reliable clinical tests and imaging studies, and consistently effective treatments. This article clarifies these issues by presenting a model of SI joint anatomy and function, a systematic approach to the diagnosis of dysfunction, and a comprehensive treatment plan.

  3. Antibody-engineered nanoparticles selectively inhibit mesenchymal cells isolated from patients with chronic lung allograft dysfunction.

    PubMed

    Cova, Emanuela; Colombo, Miriam; Inghilleri, Simona; Morosini, Monica; Miserere, Simona; Peñaranda-Avila, Jesus; Santini, Benedetta; Piloni, Davide; Magni, Sara; Gramatica, Furio; Prosperi, Davide; Meloni, Federica

    2015-01-01

    Chronic lung allograft dysfunction represents the main cause of death after lung transplantation, and so far there is no effective therapy. Mesenchymal cells (MCs) are primarily responsible for fibrous obliteration of small airways typical of chronic lung allograft dysfunction. Here, we engineered gold nanoparticles containing a drug in the hydrophobic section to inhibit MCs, and exposing on the outer hydrophilic surface a monoclonal antibody targeting a MC-specific marker (half-chain gold nanoparticles with everolimus). Half-chain gold nanoparticles with everolimus have been synthesized and incubated with MCs to evaluate the effect on proliferation and apoptosis. Drug-loaded gold nanoparticles coated with the specific antibody were able to inhibit proliferation and induce apoptosis without stimulating an inflammatory response, as assessed by in vitro experiments. These findings demonstrate the effectiveness of our nanoparticles in inhibiting MCs and open new perspectives for a local treatment of chronic lung allograft dysfunction.

  4. The changing proliferation threat

    SciTech Connect

    Sopko, J.F.

    1996-12-31

    Technological advances and new adversaries with new motives have reduced the relevancy and effectiveness of the American nonproliferation strategy that was developed during the Cold War. The Cold War`s end and the breakup of the Soviet Union have created new proliferation dangers even as they have reduced others. The familiar balance of nuclear terror that linked the superpowers and their client states for nearly 50 years in a choreographed series of confrontations has given way to a much less predictable situation, where weapons of unthinkable power appear within the grasp of those more willing to use them. Rogue nations and {open_quotes}clientless{close_quotes} states, terrorist groups, religious cults, ethnic minorities, disaffected political groups, and even individuals appear to have jointed a new arms race toward mass destruction. The author describes recent events that suggest the new trends and a serious challenge to US national security.

  5. Retinal angiomatous proliferation.

    PubMed

    Marticorena, J; Di Leva, V; Cennamo, G L; de Crecchio, G

    2011-02-01

    Retinal angiomatous proliferation (RAP) is a distinct form of choroidal neovascularization which may complicate a wet age related macular degeneration (AMD). This exudative-AMD has a peculiar clinical history and prognosis. RAP accounts from 8% to 22% of newly diagnosed cases among patients previously diagnosed as exudative AMD, and up to 25% of the occult or minimally classic CNV. The disease is more prevalent in women (90% of cases) and in elderly patients (around 75 years), and is characterized by a very poor prognosis. The neovascular process, whose retinal or choroidal origin is still object of discussion, often hesitates in the formation of a disciform scar, that evolves into a severe loss of central vision. Treatment for RAP is not yet well established; herein are described the most used therapeutic strategies, starting from laser photocoagulation until the nearest anti VEGF. The opportunity of combination among various treatments to obtain a better effectiveness and a lower frequency of recurrence is also discussed.

  6. Full-length PGC-1α salvages the phenotype of a mouse model of human neuropathy through mitochondrial proliferation.

    PubMed

    Rona-Voros, Krisztina; Eschbach, Judith; Vernay, Aurélia; Wiesner, Diana; Schwalenstocker, Birgit; Geniquet, Pauline; Mousson De Camaret, Bénédicte; Echaniz-Laguna, Andoni; Loeffler, Jean-Philippe; Ludolph, Albert C; Weydt, Patrick; Dupuis, Luc

    2013-12-20

    Increased mitochondrial mass, commonly termed mitochondrial proliferation, is frequently observed in many human diseases directly or indirectly involving mitochondrial dysfunction. Mitochondrial proliferation is thought to counterbalance a compromised energy metabolism, yet it might also be detrimental through alterations of mitochondrial regulatory functions such as apoptosis, calcium metabolism or oxidative stress. Here, we show that prominent mitochondrial proliferation occurs in Cramping mice, a model of hereditary neuropathy caused by a mutation in the dynein heavy chain gene Dync1h1. The mitochondrial proliferation correlates with post-prandial induction of full-length (FL) and N-terminal truncated (NT) isoforms of the transcriptional co-activator PGC-1α. The selective knock-out of FL-PGC-1α isoform, preserving expression and function of NT-PGC-1α, led to a complete reversal of mitochondrial proliferation. Moreover, FL-PGC-1α ablation potently exacerbated the mitochondrial dysfunction and led to severe weight loss. Finally, FL-PGC-1α ablation triggered pronounced locomotor dysfunction, tremors and inability to rear in Cramping mice. In summary, endogenous FL-PGC-1α activates mitochondrial proliferation and salvages neurological and metabolic health upon disease. NT-PGC-1α cannot fulfil this protective action. Activation of this endogenous salvage pathway might thus be a valuable therapeutic target for diseases involving mitochondrial dysfunction.

  7. Intracellular proliferation of S. aureus in osteoblasts and effects of rifampicin and gentamicin on S. aureus intracellular proliferation and survival.

    PubMed

    Mohamed, W; Sommer, U; Sethi, S; Domann, E; Thormann, U; Schütz, I; Lips, K S; Chakraborty, T; Schnettler, R; Alt, V

    2014-10-23

    Staphylococcus aureus is the most clinically relevant pathogen regarding implant-associated bone infection and its capability to invade osteoblasts is well known. The aim of this study was to investigate firstly whether S. aureus is not only able to invade but also to proliferate within osteoblasts, secondly to delineate the mechanism of invasion and thirdly to clarify whether rifampicin or gentamicin can inhibit intracellular proliferation and survival of S. aureus. The SAOS-2 osteoblast-like cell line and human primary osteoblasts were infected with S. aureus EDCC5055 and S. aureus Rosenbach 1884. Both S. aureus strains were able to invade efficiently and to proliferate within human osteoblasts. Immunofluorescence microscopy showed intracellular invasion of S. aureus and transmission electron microscopy images could demonstrate bacterial division as a sign of intracellular proliferation as well as cytosolic bacterial persistence. Cytochalasin D, the major actin depolymerisation agent, was able to significantly reduce S. aureus invasion, suggesting that invasion was enabled by promoting actin rearrangement at the cell surface. 7.5 μg/mL of rifampicin was able to inhibit bacterial survival in SAOS-2 cells with almost complete elimination of bacteria after 4 h. Gentamicin could also kill intracellular S. aureus in a dose-dependent manner, an effect that was significantly lower than that observed using rifampicin. In conclusion, S. aureus is not only able to invade but also to proliferate in osteoblasts. Invasion seems to be associated with actin rearrangement at the cell surface. Rifampicin is effective in intracellular eradication of S. aureus whereas gentamicin only poorly eliminates intracellularly replicating bacteria.

  8. Endothelial dysfunction - a major mediator of diabetic vascular disease.

    PubMed

    Sena, Cristina M; Pereira, Ana M; Seiça, Raquel

    2013-12-01

    The vascular endothelium is a multifunctional organ and is critically involved in modulating vascular tone and structure. Endothelial cells produce a wide range of factors that also regulate cellular adhesion, thromboresistance, smooth muscle cell proliferation, and vessel wall inflammation. Thus, endothelial function is important for the homeostasis of the body and its dysfunction is associated with several pathophysiological conditions, including atherosclerosis, hypertension and diabetes. Patients with diabetes invariably show an impairment of endothelium-dependent vasodilation. Therefore, understanding and treating endothelial dysfunction is a major focus in the prevention of vascular complications associated with all forms of diabetes mellitus. The mechanisms of endothelial dysfunction in diabetes may point to new management strategies for the prevention of cardiovascular disease in diabetes. This review will focus on the mechanisms and therapeutics that specifically target endothelial dysfunction in the context of a diabetic setting. Mechanisms including altered glucose metabolism, impaired insulin signaling, low-grade inflammatory state, and increased reactive oxygen species generation will be discussed. The importance of developing new pharmacological approaches that upregulate endothelium-derived nitric oxide synthesis and target key vascular ROS-producing enzymes will be highlighted and new strategies that might prove clinically relevant in preventing the development and/or retarding the progression of diabetes associated vascular complications.

  9. The Dysfunctions of Bureaucratic Structure.

    ERIC Educational Resources Information Center

    Duttweiler, Patricia Cloud

    1988-01-01

    Numerous dysfunctions result from bureaucratic school organization, including an overemphasis on specialized tasks, routine operating rules, and formal procedures for managing teaching and learning. Such schools are characterized by numerous regulations; formal communications; centralized decision making; and sharp distinctions among…

  10. Cell proliferation is reduced in the hippocampus in schizophrenia.

    PubMed

    Allen, Katherine M; Fung, Samantha J; Weickert, Cynthia Shannon

    2016-05-01

    The molecular and cellular basis of structural and functional abnormalities of the hippocampus found in schizophrenia is currently unclear. Postnatal neurogenesis contributes to hippocampal function in animal models and is correlated with hippocampal volume in primates. Reduced hippocampal cell proliferation has been previously reported in schizophrenia, which may contribute to hippocampal dysfunction. We measured the cell proliferation marker, Ki67, in post-mortem hippocampal tissue from patients with schizophrenia (n = 10) and matched controls (n = 16). Ki67-labelled cells were counted within the dentate gyrus and hilus on sections taken from the anterior hippocampus. We replicated the finding of a significant reduction in Ki67+ cells/mm² in schizophrenia cases compared to controls (t24 = 2.1, p = 0.023). In our relatively small sample, we did not find a relationship between Ki67+ cells and age overall, or between Ki67 + cells and duration of illness or antipsychotic treatment in people with schizophrenia. Our results confirm that reduced hippocampal cell proliferation may be present in schizophrenia. Restoring hippocampal neurogenesis may be a potential therapeutic target for the treatment of hippocampal dysfunction in schizophrenia. © The Royal Australian and New Zealand College of Psychiatrists 2015.

  11. Cell proliferation is reduced in the hippocampus in schizophrenia

    PubMed Central

    Allen, Katherine M; Fung, Samantha J; Shannon Weickert, Cynthia

    2015-01-01

    Objective: The molecular and cellular basis of structural and functional abnormalities of the hippocampus found in schizophrenia is currently unclear. Postnatal neurogenesis contributes to hippocampal function in animal models and is correlated with hippocampal volume in primates. Reduced hippocampal cell proliferation has been previously reported in schizophrenia, which may contribute to hippocampal dysfunction. Method: We measured the cell proliferation marker, Ki67, in post-mortem hippocampal tissue from patients with schizophrenia (n = 10) and matched controls (n = 16). Ki67-labelled cells were counted within the dentate gyrus and hilus on sections taken from the anterior hippocampus. Results: We replicated the finding of a significant reduction in Ki67+ cells/mm2 in schizophrenia cases compared to controls (t24 = 2.1, p = 0.023). In our relatively small sample, we did not find a relationship between Ki67+ cells and age overall, or between Ki67 + cells and duration of illness or antipsychotic treatment in people with schizophrenia. Conclusion: Our results confirm that reduced hippocampal cell proliferation may be present in schizophrenia. Restoring hippocampal neurogenesis may be a potential therapeutic target for the treatment of hippocampal dysfunction in schizophrenia. PMID:26113745

  12. Thyroid dysfunction and pregnancy outcomes

    PubMed Central

    Nazarpour, Sima; Ramezani Tehrani, Fahimeh; Simbar, Masoumeh; Azizi, Fereidoun

    2015-01-01

    Background: Pregnancy has a huge impact on the thyroid function in both healthy women and those that have thyroid dysfunction. The prevalence of thyroid dysfunction in pregnant women is relatively high. Objective: The objective of this review was to increase awareness and to provide a review on adverse effect of thyroid dysfunction including hyperthyroidism, hypothyroidism and thyroid autoimmune positivity on pregnancy outcomes. Materials and Methods: In this review, Medline, Embase and the Cochrane Library were searched with appropriate keywords for relevant English manuscript. We used a variety of studies, including randomized clinical trials, cohort (prospective and retrospective), case-control and case reports. Those studies on thyroid disorders among non-pregnant women and articles without adequate quality were excluded. Results: Overt hyperthyroidism and hypothyroidism has several adverse effects on pregnancy outcomes. Overt hyperthyroidism was associated with miscarriage, stillbirth, preterm delivery, intrauterine growth retardation, low birth weight, preeclampsia and fetal thyroid dysfunction. Overt hypothyroidism was associated with abortion, anemia, pregnancy-induced hypertension, preeclampsia, placental abruption, postpartum hemorrhage, premature birth, low birth weight, intrauterine fetal death, increased neonatal respiratory distress and infant neuro developmental dysfunction. However the adverse effect of subclinical hypothyroidism, and thyroid antibody positivity on pregnancy outcomes was not clear. While some studies demonstrated higher chance of placental abruption, preterm birth, miscarriage, gestational hypertension, fetal distress, severe preeclampsia and neonatal distress and diabetes in pregnant women with subclinical hypothyroidism or thyroid autoimmunity; the other ones have not reported these adverse effects. Conclusion: While the impacts of overt thyroid dysfunction on feto-maternal morbidities have been clearly identified and its long

  13. Nivolumab-induced thyroid dysfunction.

    PubMed

    Tanaka, Ryota; Fujisawa, Yasuhiro; Maruyama, Hiroshi; Nakamura, Yasuhiro; Yoshino, Koji; Ohtsuka, Mikio; Fujimoto, Manabu

    2016-06-01

    Nivolumab (ONO-4538) is an anti-programmed death-1 specific monoclonal antibody, which has become a standard treatment for metastatic malignant melanoma. Nivolumab induces autoimmune adverse events, defined as immune-related adverse events. Herein, we report a case of nivolumab-induced thyroid dysfunction in the clinical setting. Fourteen patients were treated with nivolumab at our institute, of which three developed thyroid dysfunction, an incidence higher than previously reported in the initial clinical trials. Interestingly, one patient achieved complete remission; suggesting that in some patients, the occurrence of immune-related adverse events, including thyroid dysfunction, might reflect the drug's antitumour efficacy. No patient died or discontinued nivolumab treatment owing to thyroid dysfunction. Although thyroid dysfunction first appeared to be asymptomatic, two of the three patients developed symptoms related to hypothyroidism soon after, requiring hormone replacement therapy. Another patient developed hyperthyroidism that was initially asymptomatic; the patient subsequently developed myalgia with fever >39.5°C after two additional courses of nivolumab. Treatment with nivolumab was therefore discontinued, and treatment with prednisolone was initiated. Symptoms resolved within a few days, and thyroid function normalized. Thyroid dysfunction is sometimes difficult to diagnose because its symptoms similar to those of many other diseases. In addition, thyroid-related immune-related adverse events may present with unique symptoms such as myalgia with high fever, abruptly worsening patients' quality of life. Consequently, thyroid dysfunction should be considered as a possible immune-related adverse event. Thus, it is important to test for thyroid dysfunction at baseline and before the administration of each nivolumab dose if possible.

  14. Obesity, inflammation and endothelial dysfunction.

    PubMed

    Iantorno, M; Campia, U; Di Daniele, N; Nistico, S; Forleo, G B; Cardillo, C; Tesauro, M

    2014-01-01

    Cardiovascular disease is the leading cause of morbidity and mortality in obese individuals. Obesity dramatically increases the risk of development of metabolic and cardiovascular disease. This risk appears to originate from disruption in adipose tissue function leading to a chronic inflammatory state and to dysregulation of the endocrine and paracrine actions of adipocyte-derived factors. These, in turn, impair vascular homeostasis and lead to endothelial dysfunction. An altered endothelial cell phenotype and endothelial dysfunction are common among all obesity-related complications. A crucial aspect of endothelial dysfunction is reduced nitric oxide (NO) bioavailability. A systemic pro-inflammatory state in combination with hyperglycemia, insulin resistance, oxidative stress and activation of the renin angiotensin system are systemic disturbances in obese individuals that contribute independently and synergistically to decreasing NO bioavailability. On the other hand, pro-inflammatory cytokines are locally produced by perivascular fat and act through a paracrine mechanism to independently contribute to endothelial dysfunction and smooth muscle cell dysfunction and to the pathogenesis of vascular disease in obese individuals. The promising discovery that obesity-induced vascular dysfunction is, at least in part, reversible, with weight loss strategies and drugs that promote vascular health, has not been sufficiently proved to prevent the cardiovascular complication of obesity on a large scale. In this review we discuss the pathophysiological mechanisms underlying inflammation and vascular damage in obese patients.

  15. Sirolimus-associated proteinuria and renal dysfunction.

    PubMed

    Rangan, Gopala K

    2006-01-01

    Sirolimus is a novel immunosuppressant with potent antiproliferative actions through its ability to inhibit the raptor-containing mammalian target of rapamycin protein kinase. Sirolimus represents a major therapeutic advance in the prevention of acute renal allograft rejection and chronic allograft nephropathy. Its role in the therapy of glomerulonephritis, autoimmunity, cystic renal diseases and renal cancer is under investigation. Because sirolimus does not share the vasomotor renal adverse effects exhibited by calcineurin inhibitors, it has been designated a 'non-nephrotoxic drug'. However, clinical reports suggest that, under some circumstances, sirolimus is associated with proteinuria and acute renal dysfunction. A common risk factor appears to be presence of pre-existing chronic renal damage. The mechanisms of sirolimus-associated proteinuria are multifactorial and may be due to an increase in glomerular capillary pressure following calcineurin inhibitor withdrawal. It has also been suggested that sirolimus directly causes increased glomerular permeability/injury, but evidence for this mechanism is currently inconclusive. The acute renal dysfunction associated with sirolimus (such as in delayed graft function) may be due to suppression of compensatory renal cell proliferation and survival/repair processes. Although these adverse effects occur in some patients, their occurrence could be minimised by knowledge of the molecular effects of sirolimus on the kidney, the use of sirolimus in appropriate patient populations, close monitoring of proteinuria and renal function, use of angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers if proteinuria occurs and withdrawal if needed. Further long-term analysis of renal allograft studies using sirolimus as de novo immunosuppression along with clinical and laboratory studies will refine these issues in the future.

  16. Mitochondrial Regulation of Cell Cycle and Proliferation

    PubMed Central

    Antico Arciuch, Valeria Gabriela; Elguero, María Eugenia; Poderoso, Juan José

    2012-01-01

    Abstract Eukaryotic mitochondria resulted from symbiotic incorporation of α-proteobacteria into ancient archaea species. During evolution, mitochondria lost most of the prokaryotic bacterial genes and only conserved a small fraction including those encoding 13 proteins of the respiratory chain. In this process, many functions were transferred to the host cells, but mitochondria gained a central role in the regulation of cell proliferation and apoptosis, and in the modulation of metabolism; accordingly, defective organelles contribute to cell transformation and cancer, diabetes, and neurodegenerative diseases. Most cell and transcriptional effects of mitochondria depend on the modulation of respiratory rate and on the production of hydrogen peroxide released into the cytosol. The mitochondrial oxidative rate has to remain depressed for cell proliferation; even in the presence of O2, energy is preferentially obtained from increased glycolysis (Warburg effect). In response to stress signals, traffic of pro- and antiapoptotic mitochondrial proteins in the intermembrane space (B-cell lymphoma-extra large, Bcl-2-associated death promoter, Bcl-2 associated X-protein and cytochrome c) is modulated by the redox condition determined by mitochondrial O2 utilization and mitochondrial nitric oxide metabolism. In this article, we highlight the traffic of the different canonical signaling pathways to mitochondria and the contributions of organelles to redox regulation of kinases. Finally, we analyze the dynamics of the mitochondrial population in cell cycle and apoptosis. Antioxid. Redox Signal. 16, 1150–1180. PMID:21967640

  17. Biofilms’ Role in Planktonic Cell Proliferation

    PubMed Central

    Bester, Elanna; Wolfaardt, Gideon M.; Aznaveh, Nahid B.; Greener, Jesse

    2013-01-01

    The detachment of single cells from biofilms is an intrinsic part of this surface-associated mode of bacterial existence. Pseudomonas sp. strain CT07gfp biofilms, cultivated in microfluidic channels under continuous flow conditions, were subjected to a range of liquid shear stresses (9.42 mPa to 320 mPa). The number of detached planktonic cells was quantified from the effluent at 24-h intervals, while average biofilm thickness and biofilm surface area were determined by confocal laser scanning microscopy and image analysis. Biofilm accumulation proceeded at the highest applied shear stress, while similar rates of planktonic cell detachment was maintained for biofilms of the same age subjected to the range of average shear rates. The conventional view of liquid-mediated shear leading to the passive erosion of single cells from the biofilm surface, disregards the active contribution of attached cell metabolism and growth to the observed detachment rates. As a complement to the conventional conceptual biofilm models, the existence of a biofilm surface-associated zone of planktonic cell proliferation is proposed to highlight the need to expand the traditional perception of biofilms as promoting microbial survival, to include the potential of biofilms to contribute to microbial proliferation. PMID:24201127

  18. Clinical effects of bovine lactoferrin on two canine cases with familial neutrophil dysfunction.

    PubMed

    Sato, Reeko; Kobayashi, Saori; Abe, Yuya; Kamishina, Hiroaki; Oda, Shinichi; Yasuda, Jun; Sasaki, Juso

    2012-09-01

    This study reported detailed clinical effects of bovine lactoferrin on 2 canine littermates (1 female and 1 male) with familial neutrophil dysfunction and an investigation of their genetic background. Clinical signs caused by severe upper respiratory bacterial infections were observed in these dogs. Oral administration of bovine lactoferrin for a long duration improved their clinical signs (severe uveitis in the female dog and coughing from pneumonia in the male dog). Their backcross dogs that have the same father didn't show clinical signs of bacterial infection. Neutrophil function tests revealed that the backcross dogs didn't have any disorders. It is likely that abnormal clinical signs are associated with neutrophil dysfunction in the colony, and the mother dog of these cases might be the genetic carrier of this dysfunction.

  19. Diverging roles of bacterial siderophores during infection.

    PubMed

    Holden, Victoria I; Bachman, Michael A

    2015-06-01

    Siderophores are low molecular weight, high affinity iron chelating molecules that are essential virulence factors in many Gram-negative bacterial pathogens. Whereas the chemical structure of siderophores is extremely variable, the function of siderophores has been narrowly defined as the chelation and delivery of iron to bacteria for proliferation. The discovery of the host protein Lipocalin 2, capable of specifically sequestering the siderophore Enterobactin but not its glycosylated-derivative Salmochelin, indicated that diversity in structure could be an immune evasion mechanism that provides functional redundancy during infection. However, there is growing evidence that siderophores are specialized in their iron-acquisition functions, can perturb iron homeostasis in their hosts, and even bind non-iron metals to promote bacterial fitness. The combination of siderophores produced by a pathogen can enable inter-bacterial competition, modulate host cellular pathways, and determine the bacterial "replicative niche" during infection. This review will examine both classical and novel functions of siderophores to address the concept that siderophores are non-redundant virulence factors used to enhance bacterial pathogenesis.

  20. The bacterial pathogenesis and treatment of pouchitis

    PubMed Central

    McLaughlin, S. D.; Clark, S. K.; Tekkis, P. P.; Nicholls, R. J.; Ciclitira, P. J.

    2010-01-01

    Restorative proctocolectomy (RPC) with ileal pouch-anal anastomosis is the operation of choice for patients with ulcerative colitis. Pouchitis is the most common cause of pouch dysfunction. Although the pathogenesis of this disease is not well understood, bacteria have been implicated in the disease process. Numerous bacterial studies have been reported over the last 25 years with few unifying findings. In addition, many different treatments for pouchitis have been reported with varying results. Antibiotic treatment remains the most studied and is the mainstay of treatment. In this article we review the aetiology of pouchitis and the evidenced-based treatment options. PMID:21180613

  1. Vertical nuclear proliferation.

    PubMed

    Sidel, Victor W

    2007-01-01

    All the nuclear-weapon states are working to develop new nuclear-weapon systems and upgrade their existing ones. Although the US Congress has recently blocked further development of small nuclear weapons and earth-penetrating nuclear weapons, the United States is planning a range of new warheads under the Reliable Replacement Warhead programme, and renewing its nuclear weapons infrastructure. The United Kingdom is spending 1 billion pounds sterling on updating the Atomic Weapons Establishment at Aldermaston, and about 20 billion pounds sterling on replacing its Vanguard submarines and maintaining its Trident warhead stockpile. The US has withdrawn from the Anti-Ballistic Missile Treaty and plans to install missile defence systems in Poland and the Czech Republic; Russia threatens to upgrade its nuclear countermeasures. The nuclear-weapon states should comply with their obligations under Article VI of the Non-Proliferation Treaty, as summarised in the 13-point plan agreed at the 2000 NPT Review Conference, and they should negotiate a Nuclear Weapons Convention.

  2. Endothelial dysfunction in morbid obesity.

    PubMed

    Mauricio, Maria Dolores; Aldasoro, Martin; Ortega, Joaquin; Vila, José María

    2013-01-01

    Morbid obesity is a chronic multifunctional disease characterized by an accumulation of fat. Epidemiological studies have shown that obesity is associated with cardiovascular and metabolic disorders. Endothelial dysfunction, as defined by an imbalance between relaxing and contractile endothelial factors, plays a central role in the pathogenesis of these cardiometabolic diseases. Diminished bioavailability of nitric oxide (NO) contributes to endothelial dysfunction and impairs endothelium- dependent vasodilatation. But this is not the only mechanism that drives to endothelial dysfunction. Obesity has been associated with a chronic inflammatory process, atherosclerosis, and oxidative stress. Moreover levels of asymmetrical dimethyl-L-arginine (ADMA), an endogenous inhibitor of endothelial nitric oxide synthase (eNOS), are elevated in obesity. On the other hand, increasing prostanoid-dependent vasoconstriction and decreasing vasodilator prostanoids also lead to endothelial dysfunction in obesity. Other mechanisms related to endothelin-1 (ET-1) or endothelium derived hyperpolarizing factor (EDHF) have been proposed. Bariatric surgery (BS) is a safe and effective means to achieve significant weight loss, but its use is limited only to patients with severe obesity including morbid obesity. BS also proved efficient in endothelial dysfunction reduction improving cardiovascular and metabolic comorbidities associated with morbid obesity such as diabetes, coronary artery disease, nonalcoholic fatty liver disease and cancer. This review will provide a brief overview of the mechanisms that link obesity with endothelial dysfunction, and how weight loss is a cornerstone treatment for cardiovascular comorbidities obesity-related. A better understanding of the mechanisms of obesity-induced endothelial dysfunction may help develop new therapeutic strategies to reduce cardiovascular morbidity and mortality.

  3. Human cancer: is it linked to dysfunctional lipid metabolism?

    PubMed

    Hashmi, Sarwar; Wang, Yi; Suman, Devi S; Parhar, Ranjit S; Collison, Kate; Conca, Walter; Al-Mohanna, Futwan; Gaugler, Randy

    2015-02-01

    Lipid metabolism dysfunction leading to excess fat deposits (obesity) may cause tumor (cancer) development. Both obesity and cancer are the epicenter of important medical issues. Lipid metabolism and cell death/proliferation are controlled by biochemical and molecular pathways involving many proteins, and organelles; alteration in these pathways leads to fat accumulation or tumor growth. Mammalian Krüppel-like factors, KLFs play key roles in both lipid metabolism and tumor development. Substantial epidemiological and clinical studies have established strong association of obesity with a number of human cancers. However, we need more experimental verification to determine the exact role of this metabolic alteration in the context of tumor development. A clear understanding of molecules, pathways and the mechanisms involved in lipid metabolism and cell death/proliferation will have important implications in pathogenesis, and prevention of these diseases. The regulatory role of KLFs, in both cell death/proliferation and lipid metabolism suggests a common regulation of both processes. This provides an excellent model for delivering a precise understanding of the mechanisms linking altered expression of KLFs to obesity and tumor development. Currently, mouse and rats are the models of choice for investigating disease mechanisms and pharmacological therapies but a genetic model is needed for a thorough examination of KLF function in vivo during the development of an organism. The worm Caenorhabditis elegans is an ideal model to study the connectivity between lipid metabolism and cell death/proliferation. Copyright © 2014 Elsevier B.V. All rights reserved.

  4. Swallowing Dysfunction After Critical Illness

    PubMed Central

    White, S. David; Moss, Marc

    2014-01-01

    Critical care practitioners must frequently make decisions about their patients’ ability to swallow food, liquids, and pills. These decisions can be particularly difficult given the incompletely defined epidemiology, diagnostic criteria, and prognostic features of swallowing disorders in critically ill patients. Furthermore, the consequences of improper decisions—namely, aspiration, malnutrition, hunger, and thirst—can be devastating to patients and their families. This review outlines the problem of swallowing dysfunction in critically ill patients and then addresses the most clinically relevant questions that critical care practitioners face today. First, we review the epidemiology of swallowing dysfunction in critically ill patients. Next, we describe the different diagnostic tests for swallowing dysfunction and describe a general approach to the initial assessment for swallowing disorders. Finally, we explore the existing treatments for swallowing dysfunction. Given the burden of swallowing dysfunction in patients recovering from critical illness, enabling critical care practitioners to manage these disorders, while stimulating new investigation into their pathophysiology, diagnosis, and management, will enhance our care of critically ill patients. PMID:25451355

  5. Nest Material Shapes Eggs Bacterial Environment

    PubMed Central

    Ruiz-Castellano, Cristina; Tomás, Gustavo; Ruiz-Rodríguez, Magdalena; Martín-Gálvez, David; Soler, Juan José

    2016-01-01

    environmental variation associated with risk of bacterial proliferation determining the strength of such effects. Because of costs associated to nest building, birds should adjust nest building effort to expected bacterial environments during incubation, a prediction that should be further explored. PMID:26871451

  6. Focally regulated endothelial proliferation and cell death in human synovium.

    PubMed Central

    Walsh, D. A.; Wade, M.; Mapp, P. I.; Blake, D. R.

    1998-01-01

    Angiogenesis and vascular insufficiency each may support the chronic synovial inflammation of rheumatoid arthritis. We have shown by quantitative immunohistochemistry and terminal uridyl deoxynucleotide nick end labeling that endothelial proliferation and cell death indices were each increased in synovia from patients with rheumatoid arthritis compared with osteoarthritic and noninflamed controls, whereas endothelial fractional areas did not differ significantly among disease groups. Markers of proliferation were associated with foci immunoreactive for vascular endothelial growth factor and integrin alpha(v)beta3, whereas cell death was observed in foci in which immunoreactivities for these factors were weak or absent. No association was found with thrombospondin immunoreactivity. The balance between angiogenesis and vascular regression in rheumatoid synovitis may be determined by the focal expression of angiogenic and endothelial survival factors. Increased endothelial cell turnover may contribute to microvascular dysfunction and thereby facilitate persistent synovitis. Images Figure 1 Figure 3 Figure 4 PMID:9502411

  7. Mitochondrial Dysfunction in Cardiac Ageing

    PubMed Central

    Tocchi, Autumn; Quarles, Ellen K.; Basisty, Nathan; Gitari, Lemuel; Rabinovitch, Peter S.

    2015-01-01

    Cardiovascular diseases are the leading cause of death in most developed nations. While it has received the least public attention, aging is the dominant risk factor for developing cardiovascular diseases, as the prevalence of cardiovascular diseases increases dramatically with increasing age. Cardiac aging is an intrinsic process that results in impaired cardiac function, along with cellular and molecular changes. Mitochondria play a great role in these processes, as cardiac function is an energetically demanding process. In this review, we examine mitochondrial dysfunction in cardiac aging. Recent research has demonstrated that mitochondrial dysfunction can disrupt morphology, signaling pathways, and protein interactions; conversely, mitochondrial homeostasis is maintained by mechanisms that include fission/fusion, autophagy, and unfolded protein responses. Finally, we describe some of the recent findings in mitochondrial targeted treatments to help meet the challenges of mitochondrial dysfunction in aging. PMID:26191650

  8. [Sexual dysfunctions in selected endocrinopathies].

    PubMed

    Skrzypulec, Violetta; Nowosielski, Krzysztof; Drosdzol, Agnieszka; Kowalaczyk, Robert

    2005-01-01

    According to the socio-sexological reports approximately 40-45% of women and up to 30% of males may suffer from different sexual dysfunctions. The prevalence of those disorders is gradually increasing with age. Multiply numbers of endocrinopathies may influence the human sexual life. In diabetic patients all phases of the sexual responses cycle, especially orgasm, might be affected. Women diagnosed with PCOS have decreased adaptation to the sexual life, low self-esteem and perception of self sexual attractiveness. The intimacy of infertile couples has not been well described and the characteristic of particular dysfunction in sex life has not been established yet. Interdisciplinary approach, understood as treatment of the endocrinopathy accompanied with psychological and sexological counseling, seems to be the fundamental issue in the therapy of sexual dysfunctions in patients with endocrinological disorders.

  9. Obesity and pelvic floor dysfunction.

    PubMed

    Ramalingam, Kalaivani; Monga, Ash

    2015-05-01

    Obesity is associated with a high prevalence of pelvic floor disorders. Patients with obesity present with a range of urinary, bowel and sexual dysfunction problems as well as uterovaginal prolapse. Urinary incontinence, faecal incontinence and sexual dysfunction are more prevalent in patients with obesity. Uterovaginal prolapse is also more common than in the non-obese population. Weight loss by surgical and non-surgical methods plays a major role in the improvement of these symptoms in such patients. The treatment of symptoms leads to an improvement in their quality of life. However, surgical treatment of these symptoms may be accompanied by an increased risk of complications in obese patients. A better understanding of the mechanism of obesity-associated pelvic floor dysfunction is essential.

  10. Damage to Olfactory Progenitor Cells Is Involved in Cigarette Smoke-Induced Olfactory Dysfunction in Mice.

    PubMed

    Ueha, Rumi; Ueha, Satoshi; Kondo, Kenji; Sakamoto, Takashi; Kikuta, Shu; Kanaya, Kaori; Nishijima, Hironobu; Matsushima, Kouji; Yamasoba, Tatsuya

    2016-03-01

    Exposure to cigarette smoke is a major cause of olfactory dysfunction. However, the underlying mechanisms by which cigarette smoke interferes with the highly regenerative olfactory nerve system remain unclear. To investigate whether cigarette smoke induces olfactory dysfunction by disrupting cell proliferation and cell survival in the olfactory epithelium (OE), we developed a mouse model of smoking that involved intranasal administration of a cigarette smoke solution (CSS). Immunohistological analyses and behavioral testing showed that CSS administration during a period of 24 days reduced the number of olfactory marker protein-positive mature olfactory receptor neurons (ORNs) in the OE and induced olfactory dysfunction. These changes coincided with a reduction in the number of SOX2(+) ORN progenitors and Ki-67(+) proliferating cells in the basal layer of the OE, an increase in the number of caspase-3(+) apoptotic cells, and an increase in the expression of mRNA for the inflammatory cytokines IL-1β and IL-6. Notably, the proliferating ORN progenitor population recovered after cessation of treatment with CSS, resulting in the subsequent restoration of mature ORN numbers and olfaction. These results suggest that SOX2(+) ORN progenitors are targets of CSS-induced impairment of the OE, and that by damaging the ORN progenitor population and increasing ORN death, CSS exposure eventually overwhelms the regenerative capacity of the epithelium, resulting in reduced numbers of mature ORNs and olfactory dysfunction.

  11. Autophagy-independent senescence and genome instability driven by targeted telomere dysfunction.

    PubMed

    Mar, Florie A; Debnath, Jayanta; Stohr, Bradley A

    2015-01-01

    Telomere dysfunction plays a complex role in tumorigenesis. While dysfunctional telomeres can block the proliferation of incipient cancer clones by inducing replicative senescence, fusion of dysfunctional telomeres can drive genome instability and oncogenic genomic rearrangements. Therefore, it is important to define the regulatory pathways that guide these opposing effects. Recent work has shown that the autophagy pathway regulates both senescence and genome instability in various contexts. Here, we apply models of acute telomere dysfunction to determine whether autophagy modulates the resulting genome instability and senescence responses. While telomere dysfunction rapidly induces autophagic flux in human fibroblast cell lines, inhibition of the autophagy pathway does not have a significant impact upon the transition to senescence, in contrast to what has previously been reported for oncogene-induced senescence. Our results suggest that this difference may be explained by disparities in the development of the senescence-associated secretory phenotype. We also show that chromosome fusions induced by telomere dysfunction are comparable in autophagy-proficient and autophagy-deficient cells. Altogether, our results highlight the complexity of the senescence-autophagy interface and indicate that autophagy induction is unlikely to play a significant role in telomere dysfunction-driven senescence and chromosome fusions.

  12. Aromatase inhibitors affect vaginal proliferation and steroid hormone receptors.

    PubMed

    Kallak, Theodora Kunovac; Baumgart, Juliane; Göransson, Emma; Nilsson, Kerstin; Poromaa, Inger Sundström; Stavreus-Evers, Anneli

    2014-04-01

    Women with breast cancer who are treated with aromatase inhibitors often experience vaginal atrophy symptoms and sexual dysfunction. This work aims to study proliferation and the presence and distribution of steroid hormone receptors in vaginal biopsies in relation to vaginal atrophy and vaginal pH in women with breast cancer who are on adjuvant endocrine treatment and in healthy postmenopausal women. This is a cross-sectional study that compares postmenopausal aromatase inhibitor-treated women with breast cancer (n = 15) with tamoxifen-treated women with breast cancer (n = 16) and age-matched postmenopausal women without treatment (n = 19) or with vaginal estrogen therapy (n = 16). Immunohistochemistry was used to study proliferation and steroid hormone receptor staining intensity. Data was correlated with estrogen and androgen levels, vaginal atrophy scores, and vaginal pH. Aromatase inhibitor-treated women had a lower grade of proliferation, weaker progesterone receptor staining, and stronger androgen receptor staining, which correlated with plasma estrone levels, vaginal atrophy scores, and vaginal pH. Women with aromatase inhibitor-treated breast cancer exhibit reduced proliferation and altered steroid hormone receptor staining intensity in the vagina, which are related to clinical signs of vaginal atrophy. Although these effects are most probably attributable to estrogen suppression, a possible local inhibition of aromatase cannot be ruled out.

  13. Autonomic Dysfunctions in Parkinsonian Disorders

    PubMed Central

    Bae, Hyo-Jin; Cheon, Sang-Myung; Kim, Jae Woo

    2009-01-01

    Background and Purpose: Symptoms of autonomic dysfunctions are common in the patients with parkinsonian disorders. Because clinical features of autonomic dysfunctions are diverse, the comprehensive evaluation is essential for the appropriate management. For the appreciation of autonomic dysfunctions and the identification of differences, patients with degenerative parkinsonisms are evaluated using structured questionnaire for autonomic dysfunction (ADQ). Methods: Total 259 patients, including 192 patients with [idiopathic Parkinson’s disease (IPD, age 64.6 ± 9.6 years)], 37 with [multiple system atrophy (MSA, 62.8 ± 9.1)], 9 with [dementia with Lewy body (DLB, 73.9 ± 4.3)], and 21 with [progressive supranuclear palsy (PSP, 69.4 ± 9.6)]. The ADQ was structured for evaluation of the presence of symptoms and its severity due to autonomic dysfunction, covering gastrointestinal, urinary, sexual, cardiovascular and thermoregulatory domains. Patients were also evaluated for the orthostatic hypotension. Results: Although dementia with Lewy body (DLB) patients were oldest and duration of disease was longest in IPD, total ADQ scores of MSA and PSP (23.9 ± 12.6 and 21.1 ± 7.8) were significantly increased than that of IPD (15.1 ± 10.6). Urinary and cardiovascular symptom scores of MSA and gastrointestinal symptom score of PSP were significantly worse than those of IPD. The ratio of patient with orthostatic hypotension in IPD was 31.2% and not differed between groups (35.1% in MSA, 33.3% in DLB and 33.3% in PSP). But the systolic blood pressure dropped drastically after standing in patients with MSA and DLB than in patients with IPD and PSP. Conclusions: Patients with degenerative parkinsonism showed widespread symptoms of autonomic dysfunctions. The severity of those symptoms in patients with PSP were comparing to that of MSA patients and worse than that of IPD. PMID:24868361

  14. Estrogens and Male Lower Urinary Tract Dysfunction

    PubMed Central

    Wynder, Jalissa L.; Nicholson, Tristan M.; DeFranco, Donald B.

    2016-01-01

    Benign prostatic hyperplasia (BPH) and associated lower urinary tract symptoms (LUTS) are common clinical problems in urology and affect the majority of men at some time during their lives. The development of BPH/LUTS is associated with an increased ratio of estrogen to androgen levels, and this ratio, when mimicked in a variety of animals, induces BPH and lower urinary tract dysfunction (LUTD). While the precise molecular etiology remains unclear, estrogens have been implicated in the development and maintenance of BPH. Numerous endogenous and exogenous estrogens exist in humans. These estrogens act via multiple estrogen receptors to promote or inhibit prostatic hyperplasia and other BPH-associated processes. The prostate is an estrogen target tissue, and estrogens directly and indirectly affect growth and differentiation of prostate. The precise role of estrogen action directly affecting prostate growth and differentiation in the context of BPH is an understudied area and remains to be elucidated. Estrogens and selective estrogen receptor modulators (SERMs) have been shown to promote or inhibit prostate proliferation illustrating their potential roles in the development of BPH as therapy. More work will be required to identify estrogen signaling pathways associated with LUTD in order to develop more efficacious drugs for BPH treatment and prevention. PMID:26156791

  15. Bacterial infections in cirrhosis: A critical review and practical guidance

    PubMed Central

    Bunchorntavakul, Chalermrat; Chamroonkul, Naichaya; Chavalitdhamrong, Disaya

    2016-01-01

    Bacterial infection is common and accounts for major morbidity and mortality in cirrhosis. Patients with cirrhosis are immunocompromised and increased susceptibility to develop spontaneous bacterial infections, hospital-acquired infections, and a variety of infections from uncommon pathogens. Once infection develops, the excessive response of pro-inflammatory cytokines on a pre-existing hemodynamic dysfunction in cirrhosis further predispose the development of serious complications such as shock, acute-on-chronic liver failure, renal failure, and death. Spontaneous bacterial peritonitis and bacteremia are common in patients with advanced cirrhosis, and are important prognostic landmarks in the natural history of cirrhosis. Notably, the incidence of infections from resistant bacteria has increased significantly in healthcare-associated settings. Serum biomarkers such as procalcitonin may help to improve the diagnosis of bacterial infection. Preventive measures (e.g., avoidance, antibiotic prophylaxis, and vaccination), early recognition, and proper management are required in order to minimize morbidity and mortality of infections in cirrhosis. PMID:26962397

  16. Demonstrating Bacterial Flagella.

    ERIC Educational Resources Information Center

    Porter, John R.; And Others

    1992-01-01

    Describes an effective laboratory method for demonstrating bacterial flagella that utilizes the Proteus mirabilis organism and a special harvesting technique. Includes safety considerations for the laboratory exercise. (MDH)

  17. Demonstrating Bacterial Flagella.

    ERIC Educational Resources Information Center

    Porter, John R.; And Others

    1992-01-01

    Describes an effective laboratory method for demonstrating bacterial flagella that utilizes the Proteus mirabilis organism and a special harvesting technique. Includes safety considerations for the laboratory exercise. (MDH)

  18. Nuclear Proliferation and Grand Challenges

    ScienceCinema

    McCarthy, Kathy

    2016-07-12

    Nuclear engineer Dr. Kathy McCarthy leads systems analysis. She talks about proliferation and the grand challenges of nuclear R&D. For more information about INL energy research, visit http://www.facebook.com/idahonationallaboratory.

  19. Nuclear Proliferation and Grand Challenges

    SciTech Connect

    McCarthy, Kathy

    2009-01-01

    Nuclear engineer Dr. Kathy McCarthy leads systems analysis. She talks about proliferation and the grand challenges of nuclear R&D. For more information about INL energy research, visit http://www.facebook.com/idahonationallaboratory.

  20. A western type of bacterial gill disease

    USGS Publications Warehouse

    Fish, F.F.

    1935-01-01

    The first reference to a pathological condition of the gill tissues of salmonid fishes was made by Osburn in 1910. This author in describing a progressive infolding of the opercula of trout, commonly known to hatcherymen as "short gill covers," mentioned a marked proliferation on the gill epithelium as accompanying this condition. Osburn assumed that the club-like appearance of the gill filaments due to the proliferated epithelium was the result of continual irritation of the delicate gill tissue in the absence of the usual protection offered by the normal opercula. Although such a conclusion seems quite logical, it is also possible that Osburn was dealing with "short gill covers" complicated by the unknown bacterial gill disease which was subsequently described by Davis.

  1. Photobiomodulation on alcohol induced dysfunction

    NASA Astrophysics Data System (ADS)

    Yang, Zheng-Ping; Liu, Timon C.; Zhang, Yan; Wang, Yan-Fang

    2007-05-01

    Alcohol, which is ubiquitous today, is a major health concern. Its use was already relatively high among the youngest respondents, peaked among young adults, and declined in older age groups. Alcohol is causally related to more than 60 different medical conditions. Overall, 4% of the global burden of disease is attributable to alcohol, which accounts for about as much death and disability globally as tobacco and hypertension. Alcohol also promotes the generation of reactive oxygen species (ROS) and/or interferes with the body's normal defense mechanisms against these compounds through numerous processes, particularly in the liver. Photobiomodulation (PBM) is a cell-specific effect of low intensity monochromatic light or low intensity laser irradiation (LIL) on biological systems. The cellular effects of both alcohol and LIL are ligand-independent so that PBM might rehabilitate alcohol induced dysfunction. The PBM on alcohol induced human neutrophil dysfunction and rat chronic atrophic gastritis, the laser acupuncture on alcohol addiction, and intravascular PBM on alcoholic coma of patients and rats have been observed. The endonasal PBM (EPBM) mediated by Yangming channel, autonomic nervous systems and blood cells is suggested to treat alcohol induced dysfunction in terms of EPBM phenomena, the mechanism of alcohol induced dysfunction and our biological information model of PBM. In our opinion, the therapeutic effects of PBM might also be achieved on alcoholic myopathy.

  2. Cognitive dysfunction in senior pets.

    PubMed

    Crowell-Davis, Sharon L

    2008-02-01

    Aging pets can experience declines in memory, learning, perception, and awareness. These pets may be disoriented, forget previously learned behaviors, develop new fears and anxiety, or change their interactions with people. When these changes are due to cognitive dysfunction, behavioral and environmental adjustments along with medical therapy can slow the progression and keep pets active longer.

  3. Assessing mitochondrial dysfunction in cells

    PubMed Central

    Brand, Martin D.; Nicholls, David G.

    2011-01-01

    Assessing mitochondrial dysfunction requires definition of the dysfunction to be investigated. Usually, it is the ability of the mitochondria to make ATP appropriately in response to energy demands. Where other functions are of interest, tailored solutions are required. Dysfunction can be assessed in isolated mitochondria, in cells or in vivo, with different balances between precise experimental control and physiological relevance. There are many methods to measure mitochondrial function and dysfunction in these systems. Generally, measurements of fluxes give more information about the ability to make ATP than do measurements of intermediates and potentials. For isolated mitochondria, the best assay is mitochondrial respiratory control: the increase in respiration rate in response to ADP. For intact cells, the best assay is the equivalent measurement of cell respiratory control, which reports the rate of ATP production, the proton leak rate, the coupling efficiency, the maximum respiratory rate, the respiratory control ratio and the spare respiratory capacity. Measurements of membrane potential provide useful additional information. Measurement of both respiration and potential during appropriate titrations enables the identification of the primary sites of effectors and the distribution of control, allowing deeper quantitative analyses. Many other measurements in current use can be more problematic, as discussed in the present review. PMID:21726199

  4. Olfactory dysfunction and daily life.

    PubMed

    Frasnelli, Johannes; Hummel, Thomas

    2005-03-01

    The objective of the present study was to investigate the hypothesis that subjects with parosmia suffer more in their daily life than patients who experience only quantitative olfactory loss. Two hundred five outpatients of the Smell and Taste Clinic and 25 healthy controls were included. The newly developed Questionnaire of Olfactory Disorders (QOD) was administered in combination with other psychometric tests (Beck Depression Inventory, "Befindlichkeitsskala" and the Short Form-36 Health Survey) along with an olfactory test ("Sniffin' Sticks"). Results of the QOD were found to be an appropriate and valid measure of the impact of olfactory dysfunction on daily life. Patients with parosmia and quantitative olfactory dysfunction show higher rates of daily life complaints when compared to patients suffering from quantitative olfactory impairment only (QOD-PS: P=0.005). In addition, hyposmic and anosmic patients indicated significantly more complaints compared to patients with normosmia. Further, female patients seemed to suffer more from olfactory dysfunction than male patients. In conclusion, the assessment of the degree of qualitative olfactory dysfunction may be possible by the use of instruments based on questionnaires regarding daily life problems.

  5. Sexual dysfunction in infertile women

    PubMed Central

    Zare, Zahra; Amirian, Malihe; Golmakani, Nahid; Mazlom, Reza; Laal Ahangar, Mojtaba

    2016-01-01

    Background: Sexual problems have different effects on the life of people by influencing their interpersonal and marital relationships and satisfaction. Relationship between sexual dysfunctions and infertility can be mutual. Sexual dysfunction may cause difficulty conceiving but also attempts to conceive, may cause sexual dysfunction. Objective: This paper compares sexual dysfunction in fertile and infertile women. Materials and Methods: In this cross-sectional study, 110 infertile couples referring to Montasarieh Infertility Clinic and 110 fertile couples referring to five healthcare centers in Mashhad were selected by class cluster sampling method. Data collection tools included demographic questionnaire and Glombok-Rust Inventory of Sexual Satisfaction. Data were analyzed through descriptive and analytical statistical methods by SPSS. Results: There was no significant difference in total score of sexual problems and other dimensions of sexual problems (except infrequency) in fertile 28.9 (15.5) and infertile 29.0 (15.4) women. Fertile women had more infrequency than infertile women (p=0.002). Conclusion: There was no significant difference between fertile and infertile women in terms of sexual problems. Paying attention to sexual aspects of infertility and presence of programs for training of sexual skills seems necessary for couples. PMID:27200422

  6. Sepsis-induced brain dysfunction.

    PubMed

    Adam, Nicolas; Kandelman, Stanislas; Mantz, Jean; Chrétien, Fabrice; Sharshar, Tarek

    2013-02-01

    Systemic infection is often revealed by or associated with brain dysfunction, which is characterized by alteration of consciousness, ranging from delirium to coma, seizure or focal neurological signs. Its pathophysiology involves an ischemic process, secondary to impairment of cerebral perfusion and its determinants and a neuroinflammatory process that includes endothelial activation, alteration of the blood-brain barrier and passage of neurotoxic mediators. Microcirculatory dysfunction is common to these two processes. This brain dysfunction is associated with increased mortality, morbidity and long-term cognitive disability. Its diagnosis relies essentially on neurological examination that can lead to specific investigations, including electrophysiological testing or neuroimaging. In practice, cerebrospinal fluid analysis is indisputably required when meningitis is suspected. Hepatic, uremic or respiratory encephalopathy, metabolic disturbances, drug overdose, sedative or opioid withdrawal, alcohol withdrawal delirium or Wernicke's encephalopathy are the main differential diagnoses. Currently, treatment consists mainly of controlling sepsis. The effects of insulin therapy and steroids need to be assessed. Various drugs acting on sepsis-induced blood-brain barrier dysfunction, brain oxidative stress and inflammation have been tested in septic animals but not yet in patients.

  7. Pathophysiology of diabetic sexual dysfunction.

    PubMed

    Morano, S

    2003-01-01

    Sexual dysfunction is common in patients with diabetes mellitus. Vascular, neurological and hormonal alterations are involved in this complication. Many studies showed altered endothelium-dependent and neurogenic relaxations in corpus cavernosum from diabetic patients with erectile dysfunction (ED). This finding has been associated with a lack of nitric oxyde (NO) production and a significant increase in NO synthase (NOS) binding sites in penile tissues, induced by diabetes. Advanced glycation endproducts (AGEs) concur to diabetic vascular complications by quenching NO activity and by increasing the expression of mediators of vascular damage such as vascular endothelial growth factor (VEGF), possessing permeabilizing and neoangiogenic effects, and endothelin-1 (ET-1), with vaso-constricting and mitogenic action. Moreover, the differential gene expression for various growth factors in penile tissues may be involved in the pathophysiology of ED associated with diabetes. Neuropathy is also likely to be an important cause of diabetic ED: morphological alterations of autonomic nerve fibers in cavernosal tissue of patients with diabetic ED have been demonstrated. Finally, androgens enhance nNOS gene expression in the penile corpus cavernosum of rats, suggesting that they play a role in maintaining NOS activity. However, sexual dysfunctions in women with diabetes has received less attention in clinical research. Several studies suggest an increased prevalence of deficient vaginal lubrication, making sexual intercourse unpleasant. Sexual dysfunction is associated with lower overall quality of marital relation and more depressive symptoms in diabetic women.

  8. Assessing mitochondrial dysfunction in cells.

    PubMed

    Brand, Martin D; Nicholls, David G

    2011-04-15

    Assessing mitochondrial dysfunction requires definition of the dysfunction to be investigated. Usually, it is the ability of the mitochondria to make ATP appropriately in response to energy demands. Where other functions are of interest, tailored solutions are required. Dysfunction can be assessed in isolated mitochondria, in cells or in vivo, with different balances between precise experimental control and physiological relevance. There are many methods to measure mitochondrial function and dysfunction in these systems. Generally, measurements of fluxes give more information about the ability to make ATP than do measurements of intermediates and potentials. For isolated mitochondria, the best assay is mitochondrial respiratory control: the increase in respiration rate in response to ADP. For intact cells, the best assay is the equivalent measurement of cell respiratory control, which reports the rate of ATP production, the proton leak rate, the coupling efficiency, the maximum respiratory rate, the respiratory control ratio and the spare respiratory capacity. Measurements of membrane potential provide useful additional information. Measurement of both respiration and potential during appropriate titrations enables the identification of the primary sites of effectors and the distribution of control, allowing deeper quantitative analyses. Many other measurements in current use can be more problematic, as discussed in the present review.

  9. Cell Proliferation and Cytotoxicity Assays.

    PubMed

    Adan, Aysun; Kiraz, Yağmur; Baran, Yusuf

    Cell viability is defined as the number of healthy cells in a sample and proliferation of cells is a vital indicator for understanding the mechanisms in action of certain genes, proteins and pathways involved cell survival or death after exposing to toxic agents. Generally, methods used to determine viability are also common for the detection of cell proliferation. Cell cytotoxicity and proliferation assays are generally used for drug screening to detect whether the test molecules have effects on cell proliferation or display direct cytotoxic effects. Regardless of the type of cell-based assay being used, it is important to know how many viable cells are remaining at the end of the experiment. There are a variety of assay methods based on various cell functions such as enzyme activity, cell membrane permeability, cell adherence, ATP production, co-enzyme production, and nucleotide uptake activity. These methods could be basically classified into different categories: (I) dye exclusion methods such as trypan blue dye exclusion assay, (II) methods based on metabolic activity, (III) ATP assay, (IV) sulforhodamine B assay, (V) protease viability marker assay, (VI) clonogenic cell survival assay, (VII) DNA synthesis cell proliferation assays and (V) raman micro-spectroscopy. In order to choose the optimal viability assay, the cell type, applied culture conditions, and the specific questions being asked should be considered in detail. This particular review aims to provide an overview of common cell proliferation and cytotoxicity assays together with their own advantages and disadvantages, their methodologies, comparisons and intended purposes.

  10. Metabolism links bacterial biofilms and colon carcinogenesis

    PubMed Central

    Johnson, Caroline H.; Dejea, Christine M.; Edler, David; Hoang, Linh T.; Santidrian, Antonio F.; Felding, Brunhilde H.; Cho, Kevin; Wick, Elizabeth C.; Hechenbleikner, Elizabeth M.; Uritboonthai, Winnie; Goetz, Laura; Casero, Robert A.; Pardoll, Drew M.; White, James R.; Patti, Gary J.; Sears, Cynthia L.; Siuzdak, Gary

    2015-01-01

    SUMMARY Bacterial biofilms in the colon alter the host tissue microenvironment. A role for biofilms in colon cancer metabolism has been suggested but to date has not been evaluated. Using metabolomics, we investigated the metabolic influence that microbial biofilms have on colon tissues and the related occurrence of cancer. Patient-matched colon cancers and histologically normal tissues, with or without biofilms, were examined. We show the upregulation of polyamine metabolites in tissues from cancer hosts with significant enhancement of N1, N12-diacetylspermine in both biofilm positive cancer and normal tissues. Antibiotic treatment, which cleared biofilms, decreased N1, N12-diacetylspermine levels to those seen in biofilm negative tissues, indicating that host cancer and bacterial biofilm structures contribute to the polyamine metabolite pool. These results show that colonic mucosal biofilms alter the cancer metabolome, to produce a regulator of cellular proliferation and colon cancer growth potentially affecting cancer development and progression. PMID:25959674

  11. Probing bacterial cell biology using image cytometry.

    PubMed

    Cass, Julie A; Stylianidou, Stella; Kuwada, Nathan J; Traxler, Beth; Wiggins, Paul A

    2017-03-01

    Advances in automated fluorescence microscopy have made snapshot and time-lapse imaging of bacterial cells commonplace, yet fundamental challenges remain in analysis. The vast quantity of data collected in high-throughput experiments requires a fast and reliable automated method to analyze fluorescence intensity and localization, cell morphology and proliferation as well as other descriptors. Inspired by effective yet tractable methods of population-level analysis using flow cytometry, we have developed a framework and tools for facilitating analogous analyses in image cytometry. These tools can both visualize and gate (generate subpopulations) more than 70 cell descriptors, including cell size, age and fluorescence. The method is well suited to multi-well imaging, analysis of bacterial cultures with high cell density (thousands of cells per frame) and complete cell cycle imaging. We give a brief description of the analysis of four distinct applications to emphasize the broad applicability of the tool.

  12. Metabolism links bacterial biofilms and colon carcinogenesis.

    PubMed

    Johnson, Caroline H; Dejea, Christine M; Edler, David; Hoang, Linh T; Santidrian, Antonio F; Felding, Brunhilde H; Ivanisevic, Julijana; Cho, Kevin; Wick, Elizabeth C; Hechenbleikner, Elizabeth M; Uritboonthai, Winnie; Goetz, Laura; Casero, Robert A; Pardoll, Drew M; White, James R; Patti, Gary J; Sears, Cynthia L; Siuzdak, Gary

    2015-06-02

    Bacterial biofilms in the colon alter the host tissue microenvironment. A role for biofilms in colon cancer metabolism has been suggested but to date has not been evaluated. Using metabolomics, we investigated the metabolic influence that microbial biofilms have on colon tissues and the related occurrence of cancer. Patient-matched colon cancers and histologically normal tissues, with or without biofilms, were examined. We show the upregulation of polyamine metabolites in tissues from cancer hosts with significant enhancement of N(1), N(12)-diacetylspermine in both biofilm-positive cancer and normal tissues. Antibiotic treatment, which cleared biofilms, decreased N(1), N(12)-diacetylspermine levels to those seen in biofilm-negative tissues, indicating that host cancer and bacterial biofilm structures contribute to the polyamine metabolite pool. These results show that colonic mucosal biofilms alter the cancer metabolome to produce a regulator of cellular proliferation and colon cancer growth potentially affecting cancer development and progression.

  13. Mitochondrial injury and dysfunction in hypertension-induced cardiac damage

    PubMed Central

    Eirin, Alfonso; Lerman, Amir; Lerman, Lilach O.

    2014-01-01

    Hypertension remains an important modifiable risk factor for cardiovascular disease, associated with increased morbidity and mortality. Deciphering the mechanisms involved in the pathogenesis of hypertension is critical, as its prevalence continues increasing worldwide. Mitochondria, the primary cellular energy producers, are numerous in parenchymal cells of the heart, kidney, and brain, major target organs in hypertension. These membrane-bound organelles not only maintain cellular respiration but also modulate several functions of the cell including proliferation, apoptosis, generation of reactive oxygen species, and intracellular calcium homeostasis. Therefore, mitochondrial damage and dysfunction compromise overall cell functioning. In recent years, significant advances increased our understanding of mitochondrial morphology, bioenergetics, and homeostasis, and in turn of their role in several diseases, so that mitochondrial abnormalities and dysfunction have been identified in experimental models of hypertension. In this review, we summarize current knowledge of the contribution of dysfunctional mitochondria to the pathophysiology of hypertension-induced cardiac damage, as well as available evidence of mitochondrial injury-induced damage in other organs. Finally, we discuss the capability of antihypertensive therapy to ameliorate hypertensive mitochondrial injury, and the potential position of mitochondria as therapeutic targets in patients with hypertension. PMID:25385092

  14. A mechanism for trauma induced muscle wasting and immune dysfunction

    NASA Astrophysics Data System (ADS)

    Madihally, S.; Toner, M.; Yarmush, M.; Mitchell, R.

    A diverse physiological conditions lead to a hypercatabolic state marked by the loss of proteins, primarily derived from skeletal muscle. The sustained loss of proteins results in loss of muscle mass and strength, poor healing, and long-term hospitalization. These problems are further compounded by the deterioration of immunity to infection which is a leading cause of morbidity and mortality of traumatic patients. In an attempt to understand the signal propagation mechanism(s), we tested the role of Interferon-? (IFN-? ) in an animal burn injury model; IFN-? is best conceptualized as a macrophage activating protein and known to modulate a variety of intracellular processes potentially relevant to muscle wasting and immune dysfunction. Mice congenitally -deficient in IFN-? , and IFN-? -Receptor, and wild type (WT) animals treated with IFN-? neutralizing antibody received either a 20% total body surface area burn or a control sham treatment. At days 1, 2, and 7 following treatment, skeletal muscle, peripheral blood, and spleen were harvested from both groups. Overall body weight, protein turnovers, changes in the lymphocyte subpopulations and alterations in the major histocompatibility complex I expression (MHC I) and proliferation capacity of lymphocytes was measured using mixed lymphocyte reaction (MLR). These results indicate that we can prevent both muscle wasting and immune dysfunction. Based on these observations and our previous other animal model results (using insulin therapy), a novel mechanism of interactions leading to muscle wasting and immune dysfunction will be discussed. Further, implications of these findings on future research and clinical therapies will be discussed in detail.

  15. Rifaximin has minor effects on bacterial composition, inflammation and bacterial translocation in cirrhosis; A randomized trial.

    PubMed

    Kimer, Nina; Pedersen, Julie S; Tavenier, Juliette; Christensen, Jeffrey E; Busk, Troels M; Hobolth, Lise; Krag, Aleksander; Al-Soud, Waleed Abu; Mortensen, Martin S; Sørensen, Søren J; Møller, Søren; Bendtsen, Flemming

    2017-07-03

    Decompensated cirrhosis is characterized by disturbed haemodynamics, immune dysfunction, and high risk of infections. Translocation of viable bacteria and bacterial products from the gut to the blood is considered a key driver in this process. Intestinal decontamination with rifaximin may reduce bacterial translocation (BT) and decrease inflammation. In a randomized, placebo-controlled trial investigated the effects of rifaximin on inflammation and BT in decompensated cirrhosis. Fifty-four out-patients with cirrhosis and ascites were randomized, mean age 56 years (±8.4), and MELD score 12 (±3.9). Patients received rifaximin 550 mg BD (n=36) or placebo BD (n=18). Blood and faecal (n=15) sampling were conducted at baseline and after four weeks. Bacterial DNA in blood was determined by real-time qPCR 16S rRNA gene quantification. Bacterial composition in faeces was analysed by 16S rRNA gene sequencing. Circulating markers of inflammation, including TNFα, interleukin-6, 10 and 18, Stromal cell-derived factor 1-α, transforming growth factor β-1 and high sensitivity CRP, were unaltered by rifaximin treatment. Rifaximin altered abundance of bacterial taxa in blood marginally, only a decrease in Pseudomonadales was observed. In faeces, rifaximin decreased bacterial richness, but effect on particular species was not observed. Subgroup analyses on patients with severely disturbed hemodynamics (n=34); or activated LBP (n=37) revealed no effect of rifaximin. Four weeks of treatment with rifaximin had no impact on the inflammatory state and only minor effects on BT and intestinal bacterial composition in stable, decompensated cirrhosis (NCT01769040). This article is protected by copyright. All rights reserved.

  16. Testosterone therapy in erectile dysfunction.

    PubMed

    Shabsigh, R

    2004-12-01

    Studies in animals have indicated that the nitric oxide erectile pathway is testosterone-dependent. Castration induces erectile dysfunction and a reduction in nitric oxide synthase-stained nerves in erectile tissue. Furthermore, castration adversely affects penile hemodynamics and smooth muscle content, leading to veno-occlusive dysfunction. Testosterone replenishment reverses these physiological, biochemical and structural changes. Several clinical studies have demonstrated the benefits of a combination of testosterone and sildenafil. A recently published, multicenter study evaluated the safety and efficacy of testosterone gel 1% (Testogel; Schering AG, Germany/AndroGel; Solvay Pharmaceuticals) vs. placebo gel in conjunction with sildenafil, in producing an erectile response in hypogonadal men who did not respond to treatment with sildenafil alone for erectile dysfunction. The selection criteria required subjects to have had erectile dysfunction for at least 3 months, to be non-responsive to 100 mg sildenafil and to have low testosterone levels (< 400 ng/dl). The primary efficacy measurement was the mean change from baseline in the Erectile Function domain of the International Index of Erectile Function (IIEF). Secondary outcome measures included the mean change from baseline in the other domains and the total sum of the IIEF. Subjects were randomized to receive either testosterone gel + sildenafil, or placebo gel + sildenafil for 12 weeks. Testosterone therapy with testosterone gel improved the erectile response to sildenafil. Therefore, testosterone therapy may be considered for the treatment of erectile dysfunction in men with low to low-normal testosterone levels, who have failed prior treatment with sildenafil alone. Consequently, it is important to screen for hypogonadism in men who fail PDE5 inhibitors.

  17. Ventilator-induced diaphragmatic dysfunction.

    PubMed

    Petrof, Basil J; Jaber, Samir; Matecki, Stefan

    2010-02-01

    Diaphragmatic function is a major determinant of the ability to successfully wean patients from mechanical ventilation. There is increasing recognition of a condition termed ventilator-induced diaphragmatic dysfunction. The purpose of the present review is to present evidence that mechanical ventilation can itself be a cause of diaphragmatic dysfunction, to outline our current understanding of the cellular mechanisms responsible for this phenomenon, and to discuss the implications of recent research for future therapeutic strategies. Many critically ill patients demonstrate diaphragmatic weakness. A large body of evidence from animal models, and more limited data from humans, indicates that mechanical ventilation can cause muscle fiber injury and atrophy within the diaphragm. Current data support a complex underlying pathophysiology involving oxidative stress and the activation of several intracellular proteolytic pathways involved in degradation of the contractile apparatus. This includes the calpain, caspase, and ubiquitin-proteasome systems. In addition, there is a simultaneous downregulation of protein synthesis pathways. Studies in animal models suggest that future therapies may be able to specifically target these processes, whereas for the time being current preventive measures in humans are primarily based upon allowing persistent diaphragmatic activation during mechanical ventilation. Diaphragmatic dysfunction is common in mechanically ventilated patients and is a likely cause of weaning failure. Recently, there has been a great expansion in our knowledge of how mechanical ventilation can adversely affect diaphragmatic structure and function. Future studies need to better define the evolution and mechanistic basis for ventilator-induced diaphragmatic dysfunction in humans, in order to allow the development of mechanical ventilation strategies and pharmacologic agents that will decrease the incidence of ventilator-induced diaphragmatic dysfunction.

  18. NAP reduces murine microvascular endothelial cells proliferation induced by hyperglycemia.

    PubMed

    D'Amico, Agata Grazia; Scuderi, Soraya; Maugeri, Grazia; Cavallaro, Sebastiano; Drago, Filippo; D'Agata, Velia

    2014-11-01

    Hyperglycemia has been identified as a risk factor responsible for micro- and macrovascular complications in diabetes. NAP (Davunetide) is a peptide whose neuroprotective actions are widely demonstrated, although its biological role on endothelial dysfunctions induced by hyperglycemia remains uninvestigated. In the present study we hypothesized that NAP could play a protective role on hyperglycemia-induced endothelial cell proliferation. To this end we investigated the effects of NAP on an in vitro model of murine microvascular endothelial cells grown in high glucose for 7 days. The MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assay and cyclin D1 protein expression analysis revealed that NAP treatment significantly reduces viability and proliferation of the cells. Hyperglycemia induced the activation of mitogen-activated protein kinase/extracellular signal-regulated protein kinase and/or phosphatidylinositol-3 kinase/Akt pathways in a time-dependent manner. NAP treatment reduced the phosphorylation levels of ERK and AKT in cells grown in high glucose. These evidences suggest that NAP might be effective in the regulation of endothelial dysfunction induced by hyperglycemia.

  19. Vimentin in Bacterial Infections

    PubMed Central

    Mak, Tim N.; Brüggemann, Holger

    2016-01-01

    Despite well-studied bacterial strategies to target actin to subvert the host cell cytoskeleton, thus promoting bacterial survival, replication, and dissemination, relatively little is known about the bacterial interaction with other components of the host cell cytoskeleton, including intermediate filaments (IFs). IFs have not only roles in maintaining the structural integrity of the cell, but they are also involved in many cellular processes including cell adhesion, immune signaling, and autophagy, processes that are important in the context of bacterial infections. Here, we summarize the knowledge about the role of IFs in bacterial infections, focusing on the type III IF protein vimentin. Recent studies have revealed the involvement of vimentin in host cell defenses, acting as ligand for several pattern recognition receptors of the innate immune system. Two main aspects of bacteria-vimentin interactions are presented in this review: the role of vimentin in pathogen-binding on the cell surface and subsequent bacterial invasion and the interaction of cytosolic vimentin and intracellular pathogens with regards to innate immune signaling. Mechanistic insight is presented involving distinct bacterial virulence factors that target vimentin to subvert its function in order to change the host cell fate in the course of a bacterial infection. PMID:27096872

  20. Bacterial diseases affecting apple

    USDA-ARS?s Scientific Manuscript database

    Bacterial diseases of plants are usually difficult to control and often require a combination of control measures to successfully manage the disease. There are often stark differences between the means available to control bacterial diseases in annual crops versus a woody tree crop, such as apple. ...

  1. Septins and Bacterial Infection

    PubMed Central

    Torraca, Vincenzo; Mostowy, Serge

    2016-01-01

    Septins, a unique cytoskeletal component associated with cellular membranes, are increasingly recognized as having important roles in host defense against bacterial infection. A role for septins during invasion of Listeria monocytogenes into host cells was first proposed in 2002. Since then, work has shown that septins assemble in response to a wide variety of invasive bacterial pathogens, and septin assemblies can have different roles during the bacterial infection process. Here we review the interplay between septins and bacterial pathogens, highlighting septins as a structural determinant of host defense. We also discuss how investigation of septin assembly in response to bacterial infection can yield insight into basic cellular processes including phagocytosis, autophagy, and mitochondrial dynamics. PMID:27891501

  2. Links of autophagy dysfunction to inflammatory bowel disease onset

    PubMed Central

    El-Khider, Faris; McDonald, Christine

    2017-01-01

    Introduction Autophagy is a cellular stress response that plays key roles in physiological processes, such as adaptation to starvation, degradation of aberrant proteins or organelles, anti-microbial defense, protein secretion, and innate and adaptive immunity. Dysfunctional autophagy is recognized as a contributing factor in many chronic inflammatory diseases, including inflammatory bowel disease (IBD). Genetic studies have identified multiple IBD-associated risk loci that include genes required for autophagy, and several lines of evidence demonstrate that autophagy is impaired in IBD patients. How dysfunctional autophagy contributes to IBD onset is currently under investigation by researchers. Key messages Dysfunctional autophagy has been identified to play a role IBD pathogenesis by altering processes that include: (1) intracellular bacterial killing, (2) anti-microbial peptide secretion by Paneth cells, (3) pro-inflammatory cytokine production by macrophages, (4) antigen presentation by dendritic cells, (5) goblet cell function, and (6) the endoplasmic reticulum stress response in enterocytes. The overall effect of dysregulation of these processes varies by cell type, stimulus, as well as cellular context. Manipulation of the autophagic pathway may provide a new avenue in the search for effective therapies for IBD. Conclusion Autophagy plays multiple roles in IBD pathogenesis. A better understanding of the role of autophagy in IBD patients may provide better subclassification of IBD phenotypes and novel approaches to disease management. PMID:26982478

  3. Acute bacterial sinusitis in children.

    PubMed

    DeMuri, Gregory; Wald, Ellen R

    2013-10-01

    On the basis of strong research evidence, the pathogenesis of sinusitis involves 3 key factors: sinusostia obstruction, ciliary dysfunction, and thickening of sinus secretions. On the basis of studies of the microbiology of otitis media, H influenzae is playing an increasingly important role in the etiology of sinusitis, exceeding that of S pneumoniae in some areas, and b-lactamase production by H influenzae is increasing in respiratory isolates in the United States. On the basis of some research evidence and consensus,the presentation of acute bacterial sinusitis conforms to 1 of 3 predicable patterns; persistent, severe, and worsening symptoms. On the basis of some research evidence and consensus,the diagnosis of sinusitis should be made by applying strict clinical criteria. This approach will select children with upper respiratory infection symptoms who are most likely to benefit from an antibiotic. On the basis of some research evidence and consensus,imaging is not indicated routinely in the diagnosis of sinusitis. Computed tomography or magnetic resonance imaging provides useful information when complications of sinusitis are suspected. On the basis of some research evidence and consensus,amoxicillin-clavulanate should be considered asa first-line agent for the treatment of sinusitis.

  4. Rho GTPase-activating bacterial toxins: from bacterial virulence regulation to eukaryotic cell biology.

    PubMed

    Lemonnier, Marc; Landraud, Luce; Lemichez, Emmanuel

    2007-09-01

    Studies on the interactions of bacterial pathogens with their host have provided an invaluable source of information on the major functions of eukaryotic and prokaryotic cell biology. In addition, this expanding field of research, known as cellular microbiology, has revealed fascinating examples of trans-kingdom functional interplay. Bacterial factors actually exploit eukaryotic cell machineries using refined molecular strategies to promote invasion and proliferation within their host. Here, we review a family of bacterial toxins that modulate their activity in eukaryotic cells by activating Rho GTPases and exploiting the ubiquitin/proteasome machineries. This family, found in human and animal pathogenic Gram-negative bacteria, encompasses the cytotoxic necrotizing factors (CNFs) from Escherichia coli and Yersinia species as well as dermonecrotic toxins from Bordetella species. We survey the genetics, biochemistry, molecular and cellular biology of these bacterial factors from the standpoint of the CNF1 toxin, the paradigm of Rho GTPase-activating toxins produced by urinary tract infections causing pathogenic Escherichia coli. Because it reveals important connections between bacterial invasion and the host inflammatory response, the mode of action of CNF1 and its related Rho GTPase-targetting toxins addresses major issues of basic and medical research and constitutes a privileged experimental model for host-pathogen interaction.

  5. [The influence of bacterial toxins on the carcinogenesis].

    PubMed

    Stachowicz, Anna M; Łaniewski, Paweł; Jagusztyn-Krynicka, Elzbieta K

    2010-01-01

    Bacterial infections may constitute an important risk factor of developing cancer disease. Molecular mechanisms by which bacteria contribute to cancer are extremely complex and still remain not fully understood. So far, it is generally accepted that Helicobacter pylori infections are associated with induction of gastric adenocarcinoma and MALT lymphoma. Two H. pylori toxins which modulate many cellular functions are VacA and CagA. So far, CagA is the only one known bacterial oncoprotein. However, many other bacteria produce toxins or effector proteins perturbing host cell homeostasis or/and evoking chronic inflammation. Both processes may be associated with tumour formation. Bacterial toxins which interfere, with various host signal transduction pathways, deregulate processes of cell division, proliferation and differentiation and modulate apoptosis. Some toxins cause even direct DNA damage. This review discuss the potential links between action of bacterial toxins and cancer.

  6. Adult Children of Dysfunctional Families: Childhood Roles.

    ERIC Educational Resources Information Center

    Jenkins, Stephen J.; And Others

    1993-01-01

    Used retrospective accounts to compare adult children of alcoholics (ACOAs), adults who experienced stressful events in childhood not involving parental alcoholism (A-D+), and adults with no reported dysfunction in family of origin (A-D-) with regard to dysfunctional roles adopted as children. Dysfunctional role adoption was more frequent in ACOA…

  7. Boric acid inhibits human prostate cancer cell proliferation.

    PubMed

    Barranco, Wade T; Eckhert, Curtis D

    2004-12-08

    The role of boron in biology includes coordinated regulation of gene expression in mixed bacterial populations and the growth and proliferation of higher plants and lower animals. Here we report that boric acid, the dominant form of boron in plasma, inhibits the proliferation of prostate cancer cell lines, DU-145 and LNCaP, in a dose-dependent manner. Non-tumorigenic prostate cell lines, PWR-1E and RWPE-1, and the cancer line PC-3 were also inhibited, but required concentrations higher than observed human blood levels. Studies using DU-145 cells showed that boric acid induced a cell death-independent proliferative inhibition, with little effect on cell cycle stage distribution and mitochondrial function.

  8. Glutamine regulates cardiac progenitor cell metabolism and proliferation

    PubMed Central

    Salabei, Joshua K.; Lorkiewicz, Pawel K.; Holden, Candice R.; Li, Qianhong; Hong, Kyung U.; Bolli, Roberto; Bhatnagar, Aruni; Hill, Bradford G.

    2015-01-01

    Autologous transplantation of cardiac progenitor cells (CPCs) alleviates myocardial dysfunction in the damaged heart; however, the mechanisms that contribute to their reparative qualities remain poorly understood. In this study, we examined CPC metabolism to elucidate the metabolic pathways that regulate their proliferative capacity. In complete growth medium, undifferentiated CPCs isolated from adult mouse heart proliferated rapidly (Td = 13.8 h). CPCs expressed the Glut1 transporter and their glycolytic rate was increased by high extracellular glucose concentration, in the absence of insulin. Although high glucose concentrations did not stimulate proliferation, glutamine increased CPC doubling time and promoted survival under conditions of oxidative stress. In comparison with glucose, pyruvate or BSA-palmitate, glutamine, when provided as the sole metabolic substrate, increased ATP-linked and uncoupled respiration. Although fatty acids were not used as respiratory substrates when present as a sole carbon source, glutamine-induced respiration was doubled in the presence of BSA-palmitate, suggesting that glutamine stimulates fatty acid oxidation. Additionally, glutamine promoted rapid phosphorylation of the mTORC1 substrate, p70S6k, as well as retinoblastoma protein, followed by induction of cyclin D1 and cdk4. Inhibition of either mTORC1 or glutaminolysis was sufficient to diminish CPC proliferation, and provision of cell permeable α-ketoglutarate in the absence of glutamine increased both respiration and cell proliferation, indicating a key role of glutamine anaplerosis in cell growth. These findings suggest that glutamine, by enhancing mitochondrial function and stimulating mTORC1, increases CPC proliferation, and that interventions to increase glutamine uptake or oxidation may improve CPC therapy. PMID:25917428

  9. Sexual dysfunctions and psychological disorders associated with type IIIa chronic prostatitis: a clinical survey in China.

    PubMed

    Mo, Mu-Qiong; Long, Ling-Li; Xie, Wen-Lin; Chen, Sai; Zhang, Wen-Hui; Luo, Can-Qiao; Deng, Li-Wen

    2014-12-01

    Chronic prostatitis (CP) is a frequent prostate-related complaint, impacts negatively on quality of life and is mostly of unclear etiology. Increasing attention has been paid to the prevalence of sexual dysfunctions in CP patients; however, the impact of specific types of CP and the correlation of sexual dysfunctions with psychological disorders associated with CP are not well understood. Type IIIa CP is characterized by chronic pelvic pain, urination symptoms and white blood cells in expressed prostatic secretion, but free of bacterial infection. A population of 600 type IIIa CP patients were randomly selected and 40 normal man were included as the control group. Queries were conducted by urologists. The National Institute of Health Chronic Prostatitis Symptom Index (NIH-CPSI), the International Index of Erectile Function (IIEF-5) and the Symptom Checklist 90-R were used to evaluate the symptoms and severity of prostatitis, erectile dysfunctions and psychological problems, respectively. Scores of ejaculatory pain and premature ejaculation were also collected. Our study revealed that sexual dysfunctions are frequently associated with this specific type of CP. The prevalence of erectile dysfunction, premature ejaculation and ejaculatory pain was 19, 30 and 30 %, respectively. A variety of psychological problems exist among type IIIa CP patients, including depression, anxiety, somatization, obsessive-compulsive and interpersonal sensitivity. In particular, the severity of erectile dysfunctions, but not premature ejaculation and ejaculatory pain, correlated significantly with depression and anxiety. Our data indicate that a moderate level of sexual dysfunctions exists among the type IIIa CP patients, and highlight the association of depression and anxiety with erectile dysfunction in CP patients, suggestting that special attention should be paid to these psychological issues in clinical treatments of the prostatitis symptoms and the associated erectile dysfunctions.

  10. Innate immune dysfunction in inflammatory bowel disease.

    PubMed

    Gersemann, M; Wehkamp, J; Stange, E F

    2012-05-01

    The pathogenetic mechanisms that cause the two types of inflammatory bowel disease (IBD), Crohn's disease (CD) and ulcerative colitis (UC), are still under investigation. Nevertheless, there is broad agreement that luminal microbes are of particular relevance in the development of these conditions. In recent years, increasing evidence has shown that defects in the innate immunity are at the centre of both types of IBD. The innate intestinal barrier is provided by the epithelium which secretes antimicrobial peptides (so-called defensins) that are retained in the mucus layer. In ileal CD, the alpha-defensins are lacking owing to several Paneth cell defects. In colonic CD, the expression of beta-defensins is inadequate. This may be related to downregulation of the transcription factor peroxisome proliferator-activated receptor-gamma and in some cohorts is associated with a reduced HBD2 gene copy number. In UC, the mucus layer, which protects the host from the enormous amounts of luminal microbes, is defective. This is accompanied by an insufficient differentiation from intestinal stem cells towards goblet cells. All these disturbances in the gut barrier shift the balance from epithelial defence towards bacterial offence. The current treatment for CD and UC is based on suppression of this secondary inflammatory process. In future, patients may benefit from new therapeutic approaches stimulating the protective innate immune system.

  11. ABC transporters: bacterial exporters.

    PubMed Central

    Fath, M J; Kolter, R

    1993-01-01

    The ABC transporters (also called traffic ATPases) make up a large superfamily of proteins which share a common function and a common ATP-binding domain. ABC transporters are classified into three major groups: bacterial importers (the periplasmic permeases), eukaryotic transporters, and bacterial exporters. We present a comprehensive review of the bacterial ABC exporter group, which currently includes over 40 systems. The bacterial ABC exporter systems are functionally subdivided on the basis of the type of substrate that each translocates. We describe three main groups: protein exporters, peptide exporters, and systems that transport nonprotein substrates. Prototype exporters from each group are described in detail to illustrate our current understanding of this protein family. The prototype systems include the alpha-hemolysin, colicin V, and capsular polysaccharide exporters from Escherichia coli, the protease exporter from Erwinia chrysanthemi, and the glucan exporters from Agrobacterium tumefaciens and Rhizobium meliloti. Phylogenetic analysis of the ATP-binding domains from 29 bacterial ABC exporters indicates that the bacterial ABC exporters can be divided into two primary branches. One branch contains the transport systems where the ATP-binding domain and the membrane-spanning domain are present on the same polypeptide, and the other branch contains the systems where these domains are found on separate polypeptides. Differences in substrate specificity do not correlate with evolutionary relatedness. A complete survey of the known and putative bacterial ABC exporters is included at the end of the review. PMID:8302219

  12. Import catheter in erectile dysfunction.

    PubMed

    Kayigil, O; Atahan, O; Metin, A

    1997-08-01

    We propose an alternative technique for intracavernous self-injection of sodium nitroprusside for erectile dysfunction by inserting a Medtronic ImPort* catheter with a valved tip. A silicone catheter was implanted in 3 patients with psychogenic impotence. The reservoir, which is used for vasoactive agent injection, was implanted laterally to the anterosuperior iliac spine and the distal tip of the catheter was inserted into the corpora cavernosa via a subcutaneous tunnel. The injection technique was taught to the patient and the initial injection was performed 1 week later. All patients and partners were satisfied with the technique and quality of erections at a mean followup of 14 months. There were no major local complications due to catheter implantation and no systemic complications due to sodium nitroprusside injection. An alternative technique for intracavernous pharmacotherapy of inserting an ImPort catheter prevented the complications of intracavernous injections in patients with erectile dysfunction.

  13. Dysfunctional Reward Processing in Depression

    PubMed Central

    Admon, Roee; Pizzagalli, Diego A.

    2015-01-01

    Anhedonia - diminished pleasure and/or decreased reactivity to pleasurable stimuli - is a core feature of depression that frequently persists after treatment. As a result, extensive effort has been directed towards characterizing the psychological and biological processes that mediate dysfunctional reward processing in depression. Reward processing can be parsed into sub-components that include motivation, reinforcement learning, and hedonic capacity, which, according to preclinical and neuroimaging evidence, involve partially dissociable brain systems. In line with this, recent findings indicate that behavioral impairments and neural abnormalities in depression vary across distinct reward-related constructs. Ultimately, improved understanding of precise reward-related dysfunctions in depression promises to improve diagnostic and therapeutic efforts in depression. PMID:26258159

  14. Perioperative Management of Thyroid Dysfunction

    PubMed Central

    Palace, Marcia Rashelle

    2017-01-01

    Due to the manifold effects of thyroid hormone across virtually all organ systems, the complications associated with thyroid dysfunction are numerous and diverse. The stresses encountered during the perioperative period may exacerbate underlying thyroid disorders, potentially precipitating decompensation and even death. Thus, it is of the utmost importance for the clinician to comprehend the mechanisms by which thyroid disease may complicate surgery and postoperative recovery and to be cognizant of the most effective means of optimizing the status of thyrotoxic and hypothyroid patients perioperatively. This article describes the adverse effects of thyroid dysfunction as they relate to the patient undergoing both thyroid and nonthyroid surgery and recommends treatment approaches aimed at decreasing perioperative risk. PMID:28469454

  15. Early detection of tubular dysfunction.

    PubMed

    Piscator, M

    1991-11-01

    The determination of low-molecular-weight proteins in urine as a tool for early detection of damage to the proximal tubules is briefly discussed. Beta 2-microglobulin, retinol-binding protein and alpha 1-microglobulin are at present the most widely used markers for tubular dysfunction. The determination of beta 2-microglobulin has earlier been the method of choice, but due to its instability at low pH there are certain disadvantages. Available data indicate that alpha 1-microglobulin may replace beta 2-microglobulin for screening purposes. The low-molecular-weight proteins are at present the best markers for early detection of tubular dysfunction; other constituents are not as well suited for this, even if the determination of urine enzymes has its supporters.

  16. The CNS and bladder dysfunction

    PubMed Central

    Holstege, Gert; Griffiths, Derek J.

    2012-01-01

    The brain's role in the development and maintenance of bladder control is critical, although its precise role in patient-reported complaints such as urgency and urine leakage is unknown. Functional brain imaging studies have advanced our knowledge of brain activity during the micturition cycle, showing multiple neuronal circuits involved as parts of a ‘brain-bladder control network.’ Yet, new advances need to be made in order to incorporate this knowledge into existing models of neuroanatomy and of clinical syndromes of bladder dysfunction and related clinical practice. This short article explains why and how brain imaging methods are poised to achieve that goal and decode the role of the brain in widely prevalent clinical conditions related to bladder dysfunction. PMID:23091564

  17. 15 CFR 12.2 - Undue proliferation.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 15 Commerce and Foreign Trade 1 2011-01-01 2011-01-01 false Undue proliferation. 12.2 Section 12.2... proliferation. (a) Information as to possible undue proliferation. Any person or group, including a State or... possible existence of undue proliferation. Such communications should be in writing and include...

  18. 15 CFR 12.2 - Undue proliferation.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 15 Commerce and Foreign Trade 1 2012-01-01 2012-01-01 false Undue proliferation. 12.2 Section 12.2... proliferation. (a) Information as to possible undue proliferation. Any person or group, including a State or... possible existence of undue proliferation. Such communications should be in writing and include...

  19. 15 CFR 12.2 - Undue proliferation.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 15 Commerce and Foreign Trade 1 2014-01-01 2014-01-01 false Undue proliferation. 12.2 Section 12.2... proliferation. (a) Information as to possible undue proliferation. Any person or group, including a State or... possible existence of undue proliferation. Such communications should be in writing and include...

  20. 15 CFR 12.2 - Undue proliferation.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 15 Commerce and Foreign Trade 1 2013-01-01 2013-01-01 false Undue proliferation. 12.2 Section 12.2... proliferation. (a) Information as to possible undue proliferation. Any person or group, including a State or... possible existence of undue proliferation. Such communications should be in writing and include...

  1. Mitochondrial dysfunction and organophosphorus compounds

    SciTech Connect

    Karami-Mohajeri, Somayyeh; Abdollahi, Mohammad

    2013-07-01

    Organophosphorous (OPs) pesticides are the most widely used pesticides in the agriculture and home. However, many acute or chronic poisoning reports about OPs have been published in the recent years. Mitochondria as a site of cellular oxygen consumption and energy production can be a target for OPs poisoning as a non-cholinergic mechanism of toxicity of OPs. In the present review, we have reviewed and criticized all the evidences about the mitochondrial dysfunctions as a mechanism of toxicity of OPs. For this purpose, all biochemical, molecular, and morphological data were retrieved from various studies. Some toxicities of OPs are arisen from dysfunction of mitochondrial oxidative phosphorylation through alteration of complexes I, II, III, IV and V activities and disruption of mitochondrial membrane. Reductions of adenosine triphosphate (ATP) synthesis or induction of its hydrolysis can impair the cellular energy. The OPs disrupt cellular and mitochondrial antioxidant defense, reactive oxygen species generation, and calcium uptake and promote oxidative and genotoxic damage triggering cell death via cytochrome C released from mitochondria and consequent activation of caspases. The mitochondrial dysfunction induced by OPs can be restored by use of antioxidants such as vitamin E and C, alpha-tocopherol, electron donors, and through increasing the cytosolic ATP level. However, to elucidate many aspect of mitochondrial toxicity of Ops, further studies should be performed. - Highlights: • As a non-cholinergic mechanism of toxicity, mitochondria is a target for OPs. • OPs affect action of complexes I, II, III, IV and V in the mitochondria. • OPs reduce mitochondrial ATP. • OPs promote oxidative and genotoxic damage via release of cytochrome C from mitochondria. • OP-induced mitochondrial dysfunction can be restored by increasing the cytosolic ATP.

  2. Hypnotic metaphor and sexual dysfunction.

    PubMed

    Gilmore, L G

    1987-01-01

    Although hypnosis can be very effective in alleviating sexual problems, few sex therapists use hypnotic methods. This paper seeks to encourage a greater use of hypnosis among clinicians by presenting: a description of the new hypnosis exemplified in the work of Milton H. Erickson; an explanation of one of Erickson's most important and innovative methods, the use of multiple embedded metaphors; and case histories illustrating the application of hypnotic approaches to sexual dysfunction.

  3. Mitochondrial dysfunction in Parkinson's disease.

    PubMed

    Bose, Anindita; Beal, M Flint

    2016-10-01

    Parkinson's disease (PD) is the second most common neurodegenerative disease. About 2% of the population above the age of 60 is affected by the disease. The pathological hallmarks of the disease include the loss of dopaminergic neurons in the substantia nigra and the presence of Lewy bodies that are made of α-synuclein. Several theories have been suggested for the pathogenesis of PD, of which mitochondrial dysfunction plays a pivotal role in both sporadic and familial forms of the disease. Dysfunction of the mitochondria that is caused by bioenergetic defects, mutations in mitochondrial DNA, nuclear DNA gene mutations linked to mitochondria, and changes in dynamics of the mitochondria such fusion or fission, changes in size and morphology, alterations in trafficking or transport, altered movement of mitochondria, impairment of transcription, and the presence of mutated proteins associated with mitochondria are implicated in PD. In this review, we provide a detailed overview of the mechanisms that can cause mitochondrial dysfunction in PD. We bring to the forefront, new signaling pathways such as the retromer-trafficking pathway and its implication in the disease and also provide a brief overview of therapeutic strategies to improve mitochondrial defects in PD. Bioenergetic defects, mutations in mitochondrial DNA, nuclear DNA gene mutations, alterations in mitochondrial dynamics, alterations in trafficking/transport and mitochondrial movement, abnormal size and morphology, impairment of transcription and the presence of mutated proteins associated with mitochondria are implicated in PD. In this review, we focus on the mechanisms underlying mitochondrial dysfunction in PD and bring to the forefront new signaling pathways that may be involved in PD. We also provide an overview of therapeutic strategies to improve mitochondrial defects in PD. This article is part of a special issue on Parkinson disease. © 2016 International Society for Neurochemistry.

  4. Thyroid Dysfunction from Antineoplastic Agents

    PubMed Central

    Larsen, P. Reed; Marqusee, Ellen

    2011-01-01

    Unlike cytotoxic agents that indiscriminately affect rapidly dividing cells, newer antineoplastic agents such as targeted therapies and immunotherapies are associated with thyroid dysfunction. These include tyrosine kinase inhibitors, bexarotene, radioiodine-based cancer therapies, denileukin diftitox, alemtuzumab, interferon-α, interleukin-2, ipilimumab, tremelimumab, thalidomide, and lenalidomide. Primary hypothyroidism is the most common side effect, although thyrotoxicosis and effects on thyroid-stimulating hormone secretion and thyroid hormone metabolism have also been described. Most agents cause thyroid dysfunction in 20%–50% of patients, although some have even higher rates. Despite this, physicians may overlook drug-induced thyroid dysfunction because of the complexity of the clinical picture in the cancer patient. Symptoms of hypothyroidism, such as fatigue, weakness, depression, memory loss, cold intolerance, and cardiovascular effects, may be incorrectly attributed to the primary disease or to the antineoplastic agent. Underdiagnosis of thyroid dysfunction can have important consequences for cancer patient management. At a minimum, the symptoms will adversely affect the patient’s quality of life. Alternatively, such symptoms can lead to dose reductions of potentially life-saving therapies. Hypothyroidism can also alter the kinetics and clearance of medications, which may lead to undesirable side effects. Thyrotoxicosis can be mistaken for sepsis or a nonendocrinologic drug side effect. In some patients, thyroid disease may indicate a higher likelihood of tumor response to the agent. Both hypothyroidism and thyrotoxicosis are easily diagnosed with inexpensive and specific tests. In many patients, particularly those with hypothyroidism, the treatment is straightforward. We therefore recommend routine testing for thyroid abnormalities in patients receiving these antineoplastic agents. PMID:22010182

  5. Therapeutic approaches to diastolic dysfunction.

    PubMed

    Janardhanan, Rajesh; Desai, Akshay S; Solomon, Scott D

    2009-08-01

    Progressive abnormalities of passive stiffness or active relaxation of the myocardium that impair ventricular filling during diastole may be an important contributor to the development of heart failure in patients with preserved ejection fraction. In this review, we discuss the epidemiology and pathophysiology of diastolic dysfunction and heart failure with preserved ejection fraction, highlighting potential therapeutic approaches and exploring the limited available evidence base for improving clinical outcomes in patients with these challenging entities.

  6. [The evaluation of erectile dysfunction].

    PubMed

    Lehmann, Kurt

    2010-03-01

    The evaluation of erectile dysfunction should assess correctable etiologic diseases. A structured evaluation is recommended because of its semi-quantitative and reproducible nature. This evaluation primarily follows a therapy-oriented strategy. Therefore patient and physician should define treatment goals early in the course. Those treatment goals may change within the life cycle. Interview and clinical assessment are the corner stones of evaluation. Invasive testing is less important nowadays.

  7. Temporomandibular joint pain and dysfunction.

    PubMed

    Herb, Kathleen; Cho, Sung; Stiles, Marlind Alan

    2006-12-01

    Pain caused by temporomandibular disorders originates from either muscular or articular conditions, or both. Distinguishing the precise source of the pain is a significant diagnostic challenge to clinicians, and effective management hinges on establishing a correct diagnosis. This paper examines terminology and regional anatomy as it pertains to functional and dysfunctional states of the temporomandibular joint and muscles of mastication. A review of the pathophysiology of the most common disorders is provided. Trends in evaluation, diagnosis, treatment, and research are presented.

  8. Gonadal dysfunction in systemic diseases.

    PubMed

    Karagiannis, Asterios; Harsoulis, Faidon

    2005-04-01

    Gonadal function is significantly affected in many acute and chronic systemic diseases. As the function of the testes and the ovaries is determined by the integrity of the hypothalamic-pituitary-gonadal axis, it is obvious that a systemic disease may affect one or more levels of the axis in such a manner that the gonadal dysfunction may have various clinical and laboratory manifestations. In this brief review, the most common disturbances seen in the main systemic diseases will be discussed.

  9. Erectile dysfunction and cardiovascular disease

    PubMed Central

    Jackson, Graham

    2013-01-01

    The link between erectile dysfunction (ED) and cardiovascular disease (CVD) is reviewed by assessing original papers, current consensus, previous reviews and meta-analyses. The link between these conditions is confirmed, and the evaluation and assessment summarised with a new evidence-based algorithm. ED, especially in younger men, is a marker of an increased risk of CVD, and ED needs to be incorporated into all risk-screening programmes. PMID:26558084

  10. Mitochondrial dysfunction in mammalian ageing.

    PubMed

    Terzioglu, Mügen; Larsson, Nils-Göran

    2007-01-01

    Ageing is likely a multifactorial process caused by accumulated damage to a variety of cellular components. Increasing age in mammals correlates with increased levels of mitochondrial DNA (mtDNA) mutations and deteriorating respiratory chain function. Mosaic respiratory chain deficiency in a subset of cells in various tissues, such as heart, skeletal muscle, colonic crypts and neurons, is typically found in aged humans. Experimental evidence in the mouse has linked increased levels of somatic mtDNA mutations to a variety of ageing phenotypes, such as osteoporosis, hair loss, greying of the hair, weight reduction and decreased fertility. It has been known for a long time that respiratory chain-deficient cells are more prone to undergo apoptosis and increased cell loss is therefore likely of importance in age-associated mitochondrial dysfunction. There is a tendency to automatically link mitochondrial dysfunction to increased production of reactive oxygen species (ROS). However, the experimental support for this concept is rather weak. Mouse models with respiratory chain deficiency induced by tissue-specific mtDNA depletion or by massive increase of point mutations in mtDNA have very minor or no increase of oxidative stress. Future studies are needed to address the relative importance of mitochondrial dysfunction and ROS in mammalian ageing.

  11. Mitochondrial disease and endocrine dysfunction.

    PubMed

    Chow, Jasmine; Rahman, Joyeeta; Achermann, John C; Dattani, Mehul T; Rahman, Shamima

    2017-02-01

    Mitochondria are critical organelles for endocrine health; steroid hormone biosynthesis occurs in these organelles and they provide energy in the form of ATP for hormone production and trafficking. Mitochondrial diseases are multisystem disorders that feature defective oxidative phosphorylation, and are characterized by enormous clinical, biochemical and genetic heterogeneity. To date, mitochondrial diseases have been found to result from >250 monogenic defects encoded across two genomes: the nuclear genome and the ancient circular mitochondrial genome located within mitochondria themselves. Endocrine dysfunction is often observed in genetic mitochondrial diseases and reflects decreased intracellular production or extracellular secretion of hormones. Diabetes mellitus is the most frequently described endocrine disturbance in patients with inherited mitochondrial diseases, but other endocrine manifestations in these patients can include growth hormone deficiency, hypogonadism, adrenal dysfunction, hypoparathyroidism and thyroid disease. Although mitochondrial endocrine dysfunction frequently occurs in the context of multisystem disease, some mitochondrial disorders are characterized by isolated endocrine involvement. Furthermore, additional monogenic mitochondrial endocrine diseases are anticipated to be revealed by the application of genome-wide next-generation sequencing approaches in the future. Understanding the mitochondrial basis of endocrine disturbance is key to developing innovative therapies for patients with mitochondrial diseases.

  12. Adipose tissue dysfunction in obesity.

    PubMed

    Blüher, M

    2009-06-01

    The incidence of obesity has increased dramatically during recent decades. Obesity will cause a decline in life expectancy for the first time in recent history due to numerous co-morbid disorders. Adipocyte and adipose tissue dysfunction belong to the primary defects in obesity and may link obesity to several health problems including increased risk of insulin resistance, type 2 diabetes, fatty liver disease, hypertension, dyslipidemia, atherosclerosis, dementia, airway disease and some cancers. However, not all obese individuals develop obesity related metabolic or cardiovascular disorders potentially due to a preserved normal adipose tissue architecture and function. The majority of patients with obesity have an impaired adipose tissue function caused by the interaction of genetic and environmental factors which lead to adipocyte hypertrophy, hypoxia, a variety of stresses and inflammatory processes within adipose tissue. Ectopic fat accumulation including visceral obesity may be considered as a consequence of adipose tissue dysfunction, which is further characterized by changes in the cellular composition, increased lipid storage and impaired insulin sensitivity in adipocytes, and secretion of a proinflammatory, atherogenic, and diabetogenic adipokine pattern. This review focuses on the discussion of mechanisms causing or maintaining impaired adipose tissue function in obesity and potentially linking obesity to its associated disorders. A model is proposed how different pathogenic factors and mechanisms may cause dysfunction of adipose tissue.

  13. [Drug therapy of bladder dysfunction].

    PubMed

    Caremel, R; Cornu, J-N; Kerdraon, J; Castel-Lacanal, E; Bastide, C; Bruyere, F; Guy, L; Karsenty, G

    2013-11-01

    To describe drugs targeting urinary bladder to treat bladder dysfunctions such as OAB, NDO and bladder pain syndrome. Pubmed search for efficacy, mode of action and side effects for each molecule. Additional data were searched from the French regulatory agencies web sites (HAS and ANSM). Anticholinergics antimuscarinics remain the first-line treatment option for both OAB and NDO. Beta-3 adrenergics emerges as a new therapeutic class for OAB. Post approval safety as well as association with other micturition cycle's drugs need to be evaluated. Phosphodiesterase 5 inhibitors are effective to treat BPH-related LUTS including storage symptoms. Botulinum toxin type A injections within the detrusor are effective and approved to treat NDO in MS and spinal cord injured patients voiding with clean intermittent catheterization. Evaluation of such approach to treat OAB is ongoing. Drug therapy for bladder pain syndrome has limited efficacy including pentosan polyphosphate despite it has a temporary autorisation. There is no drug treatment to restore or improve bladder contraction. Armamenterium to treat bladder dysfunction has recently increased. Three new therapeutic classes emerged. Careful post approval evaluation is mandatory and study of these drugs' combination is expected. Results should drive changes in bladder dysfunction treatment algorithms. Copyright © 2013. Published by Elsevier Masson SAS.

  14. Gut dysfunction in Parkinson's disease

    PubMed Central

    Mukherjee, Adreesh; Biswas, Atanu; Das, Shyamal Kumar

    2016-01-01

    Early involvement of gut is observed in Parkinson’s disease (PD) and symptoms such as constipation may precede motor symptoms. α-Synuclein pathology is extensively evident in the gut and appears to follow a rostrocaudal gradient. The gut may act as the starting point of PD pathology with spread toward the central nervous system. This spread of the synuclein pathology raises the possibility of prion-like propagation in PD pathogenesis. Recently, the role of gut microbiota in PD pathogenesis has received attention and some phenotypic correlation has also been shown. The extensive involvement of the gut in PD even in its early stages has led to the evaluation of enteric α-synuclein as a possible biomarker of early PD. The clinical manifestations of gastrointestinal dysfunction in PD include malnutrition, oral and dental disorders, sialorrhea, dysphagia, gastroparesis, constipation, and defecatory dysfunction. These conditions are quite distressing for the patients and require relevant investigations and adequate management. Treatment usually involves both pharmacological and non-pharmacological measures. One important aspect of gut dysfunction is its contribution to the clinical fluctuations in PD. Dysphagia and gastroparesis lead to inadequate absorption of oral anti-PD medications. These lead to response fluctuations, particularly delayed-on and no-on, and there is significant relationship between levodopa pharmacokinetics and gastric emptying in patients with PD. Therefore, in such cases, alternative routes of administration or drug delivery systems may be required. PMID:27433087

  15. Pyrosequencing analysis of the bacterial community in drinking water wells.

    PubMed

    Navarro-Noya, Yendi E; Suárez-Arriaga, Mayra C; Rojas-Valdes, Aketzally; Montoya-Ciriaco, Nina M; Gómez-Acata, Selene; Fernández-Luqueño, Fabián; Dendooven, Luc

    2013-07-01

    Wells used for drinking water often have a large biomass and a high bacterial diversity. Current technologies are not always able to reduce the bacterial population, and the threat of pathogen proliferation in drinking water sources is omnipresent. The environmental conditions that shape the microbial communities in drinking water sources have to be elucidated, so that pathogen proliferation can be foreseen. In this work, the bacterial community in nine water wells of a groundwater aquifer in Northern Mexico were characterized and correlated to environmental characteristics that might control them. Although a large variation was observed between the water samples, temperature and iron concentration were the characteristics that affected the bacterial community structure and composition in groundwater wells. Small increases in the concentration of iron in water modified the bacterial communities and promoted the growth of the iron-oxidizing bacteria Acidovorax. The abundance of the genera Flavobacterium and Duganella was correlated positively with temperature and the Acidobacteria Gp4 and Gp1, and the genus Acidovorax with iron concentrations in the well water. Large percentages of Flavobacterium and Pseudomonas bacteria were found, and this is of special concern as bacteria belonging to both genera are often biofilm developers, where pathogens survival increases.

  16. Blood borne: bacterial components in mother's blood influence fetal development.

    PubMed

    Loughran, Allister J; Tuomanen, Elaine I

    2016-01-01

    Bacterial or viral infection of the mother during the course of pregnancy can cross the placenta and actively infect the fetus. However, especially for bacteria, it is more common for mothers to experience an infection that can be treated without overt fetal infection. In this setting, it is less well understood what the risk to fetal development is, particularly in terms of neurological development. This research highlight reviews recent findings indicating that bacterial components generated during infection of the mother can cross the placenta and activate the fetal innate immune system resulting in changes in the course of brain development and subsequent progression to postnatal cognitive disorders. Bacterial cell wall is a ubiquitous bacterial PAMP (pathogen-associated molecular pattern) known to activate inflammation through the stimulation of TLR2. Cell wall is released from bacteria during antibiotic treatment and new work shows that embryos exposed to cell wall from the mother demonstrate anomalous proliferation of neuronal precursor cells in a TLR2 dependent manner. Such proliferation increases the neuronal density of the cortical plate and alters brain architecture. Although there is no fetal death, subsequent cognitive development is significantly impaired. This model system suggests that bacterial infection of the mother and its treatment can impact fetal brain development and requires greater understanding to potentially eliminate a risk factor for cognitive disorders such as autism.

  17. Bile acids regulate intestinal cell proliferation by modulating EGFR and FXR signaling

    PubMed Central

    Dossa, Avafia Y.; Escobar, Oswaldo; Golden, Jamie; Frey, Mark R.; Ford, Henri R.

    2015-01-01

    Bile acids (BAs) are synthesized in the liver and secreted into the intestine. In the lumen, enteric bacteria metabolize BAs from conjugated, primary forms into more toxic unconjugated, secondary metabolites. Secondary BAs can be injurious to the intestine and may contribute to disease. The epidermal growth factor receptor (EGFR) and the nuclear farnesoid X receptor (FXR) are known to interact with BAs. In this study we examined the effects of BAs on intestinal epithelial cell proliferation and investigated the possible roles for EGFR and FXR in these effects. We report that taurine-conjugated cholic acid (TCA) induced proliferation, while its unconjugated secondary counterpart deoxycholic acid (DCA) inhibited proliferation. TCA stimulated phosphorylation of Src, EGFR, and ERK 1/2. Pharmacological blockade of any of these pathways or genetic ablation of EGFR abrogated TCA-stimulated proliferation. Interestingly, Src or EGFR inhibitors eliminated TCA-induced phosphorylation of both molecules, suggesting that their activation is interdependent. In contrast to TCA, DCA exposure diminished EGFR phosphorylation, and pharmacological or siRNA blockade of FXR abolished DCA-induced inhibition of proliferation. Taken together, these results suggest that TCA induces intestinal cell proliferation via Src, EGFR, and ERK activation. In contrast, DCA inhibits proliferation via an FXR-dependent mechanism that may include downstream inactivation of the EGFR/Src/ERK pathway. Since elevated secondary BA levels are the result of specific bacterial modification, this may provide a mechanism through which an altered microbiota contributes to normal or abnormal intestinal epithelial cell proliferation. PMID:26608185

  18. Erectile dysfunction in patients with cardiovascular disease

    PubMed Central

    Ophuis, A.J.M. Oude; Nijeholt, A.A.B. Lycklama à

    2006-01-01

    Erectile dysfunction is a highly prevalent disease, especially in cardiovascular-compromised men. Many of the well-established risk factors for cardiovascular disease are also risk factors for erectile dysfunction. A correlation between erectile dysfunction and endothelial dysfunction is well established. It is postulated that erectile dysfunction with an arteriovascular aetiology can predate and be an indicator of potential coronary artery disease. In this paper we will attempt to increase awareness among cardiologists for the predictive value of erectile dysfunction for future cardiovascular disease in order to optimise cardiovascular risk management. The treatment of erectile dysfunction and cardiovascular interactions is also discussed in detail. ImagesFigure 1AFigure 1B PMID:25696612

  19. Novel factors modulating human β-cell proliferation

    PubMed Central

    Shirakawa, Jun; Kulkarni, Rohit N.

    2016-01-01

    β-cell dysfunction in type 1 and type 2 diabetes is accompanied by a progressive loss of β-cells, and an understanding of the cellular mechanism(s) that regulate β-cell mass will enable approaches to enhance hormone secretion. It is becoming increasingly recognized that enhancement of human β-cell proliferation is one potential approach to restore β-cell mass to prevent and/or cure type 1 and type 2 diabetes. While several reports describe the factor(s) that enhance β-cell replication in animal models or cell lines, promoting effective human β-cell proliferation continues to be a challenge in the field. In this review, we discuss recent studies reporting successful human β-cell proliferation including WS6, an IκB kinase and EBP1 inhibitor; harmine and 5-IT, both DYRK1A inhibitors; GNF7156 and GNF4877, GSK-3β and DYRK1A inhibitors; osteoprotegrin and Denosmab, RANK inhibitors; and SerpinB1, a protease inhibitor. These studies provide important examples of proteins and pathways that may prove useful for designing therapeutic strategies to counter the different forms of diabetes. PMID:27615134

  20. Novel factors modulating human β-cell proliferation.

    PubMed

    Shirakawa, J; Kulkarni, R N

    2016-09-01

    β-Cell dysfunction in type 1 and type 2 diabetes is accompanied by a progressive loss of β-cells, and an understanding of the cellular mechanism(s) that regulate β-cell mass will enable approaches to enhance hormone secretion. It is becoming increasingly recognized that enhancement of human β-cell proliferation is one potential approach to restore β-cell mass to prevent and/or cure type 1 and type 2 diabetes. While several reports describe the factor(s) that enhance β-cell replication in animal models or cell lines, promoting effective human β-cell proliferation continues to be a challenge in the field. In this review, we discuss recent studies reporting successful human β-cell proliferation including WS6, an IkB kinase and EBP1 inhibitor; harmine and 5-IT, both DYRK1A inhibitors; GNF7156 and GNF4877, GSK-3β and DYRK1A inhibitors; osteoprotegrin and Denosmab, receptor activator of NF-kB (RANK) inhibitors; and SerpinB1, a protease inhibitor. These studies provide important examples of proteins and pathways that may prove useful for designing therapeutic strategies to counter the different forms of human diabetes. © 2016 John Wiley & Sons Ltd.

  1. Bacterial surface adaptation

    NASA Astrophysics Data System (ADS)

    Utada, Andrew

    2014-03-01

    Biofilms are structured multi-cellular communities that are fundamental to the biology and ecology of bacteria. Parasitic bacterial biofilms can cause lethal infections and biofouling, but commensal bacterial biofilms, such as those found in the gut, can break down otherwise indigestible plant polysaccharides and allow us to enjoy vegetables. The first step in biofilm formation, adaptation to life on a surface, requires a working knowledge of low Reynolds number fluid physics, and the coordination of biochemical signaling, polysaccharide production, and molecular motility motors. These crucial early stages of biofilm formation are at present poorly understood. By adapting methods from soft matter physics, we dissect bacterial social behavior at the single cell level for several prototypical bacterial species, including Pseudomonas aeruginosa and Vibrio cholerae.

  2. Growth of Bacterial Colonies

    NASA Astrophysics Data System (ADS)

    Warren, Mya; Hwa, Terence

    2013-03-01

    On hard agar gel, there is insufficient surface hydration for bacteria to swim or swarm. Instead, growth occurs in colonies of close-packed cells, which expand purely due to repulsive interactions: individual bacteria push each other out of the way through the force of their growth. In this way, bacterial colonies represent a new type of ``active'' granular matter. In this study, we investigate the physical, biochemical, and genetic elements that determine the static and dynamic aspects of this mode of bacterial growth for E. coli. We characterize the process of colony expansion empirically, and use discrete and continuum models to examine the extent to which our observations can be explained by the growth characteristics of non-communicating cells, coupled together by physical forces, nutrients, and waste products. Our results challenge the commonly accepted modes of bacterial colony growth and provide insight into sources of growth limitation in crowded bacterial communities.

  3. Dequalinium for bacterial vaginosis.

    PubMed

    2017-05-01

    Bacterial vaginosis is an infection characterised by overgrowth of anaerobic bacteria in the vagina with an accompanying loss of lactobacilli, and is thought to be the most common cause of abnormal vaginal discharge in women of child-bearing age.(1) Standard treatment for symptomatic bacterial vaginosis consists of a short course of an oral or topical antibiotic.(2) Dequalinium, a topical antiseptic agent, has been available for many years as a treatment for oral infections.(3) A new formulation, dequalinium 10mg vaginal tablets (Fluomizin-Kora Healthcare), was licensed in the UK in June 2015 for the treatment of bacterial vaginosis.(4) Here, we review evidence for the effectiveness and safety of dequalinium vaginal tablets in the management of bacterial vaginosis. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  4. Coaggregation between bacterial species.

    PubMed

    Kinder, S A; Holt, S C

    1994-01-01

    Bacterial coaggregation, or interbacterial adherence, is one mechanism involved in the development of bacterial biofilms that are found on surfaces in nature. Assays used to measure coaggregation rely on the interaction of bacterial cells in suspension or attachment of one species to a second species that has been fixed to a solid substrate. Both semiquantitative and quantitative assays are described. These methods have also been used to determine the nature of the adherence and molecules involved in mediating the interaction, to characterize potential inhibitors, to isolate the bacterial adhesins and receptors, and to isolate adherence-deficient mutant strains. Each of the assay systems offers different advantages, with significant variations in sensitivity. Selection of a particular assay system should depend on the goals of the study to be performed.

  5. Bacterial toxins as immunomodulators.

    PubMed

    Donaldson, David S; Williams, Neil A

    2009-01-01

    Bacterial toxins are the causative agent at pathology in a variety of diseases. Although not always the primary target of these toxins, many have been shown to have potent immunomodulatory effects, for example, inducing immune responses to co-administered antigens and suppressing activation of immune cells. These abilities of bacterial toxins can be harnessed and used in a therapeutic manner, such as in vaccination or the treatment of autoimmune diseases. Furthermore, the ability of toxins to gain entry to cells can be used in novel bacterial toxin based immuno-therapies in order to deliver antigens into MHC Class I processing pathways. Whether the immunomodulatory properties of these toxins arose in order to enhance bacterial survival within hosts, to aid spread within the population or is pure serendipity, it is interesting to think that these same toxins potentially hold the key to preventing or treating human disease.

  6. Bacterial Infections - Multiple Languages

    MedlinePlus

    ... Supplements Videos & Tools You Are Here: Home → Multiple Languages → All Health Topics → Bacterial Infections URL of this page: https://medlineplus.gov/languages/bacterialinfections.html Other topics A-Z Expand Section ...

  7. Autophagic clearance of bacterial pathogens: molecular recognition of intracellular microorganisms.

    PubMed

    Pareja, Maria Eugenia Mansilla; Colombo, Maria I

    2013-01-01

    Autophagy is involved in several physiological and pathological processes. One of the key roles of the autophagic pathway is to participate in the first line of defense against the invasion of pathogens, as part of the innate immune response. Targeting of intracellular bacteria by the autophagic machinery, either in the cytoplasm or within vacuolar compartments, helps to control bacterial proliferation in the host cell, controlling also the spreading of the infection. In this review we will describe the means used by diverse bacterial pathogens to survive intracellularly and how they are recognized by the autophagic molecular machinery, as well as the mechanisms used to avoid autophagic clearance.

  8. Autophagic clearance of bacterial pathogens: molecular recognition of intracellular microorganisms

    PubMed Central

    Mansilla Pareja, Maria Eugenia; Colombo, Maria I.

    2013-01-01

    Autophagy is involved in several physiological and pathological processes. One of the key roles of the autophagic pathway is to participate in the first line of defense against the invasion of pathogens, as part of the innate immune response. Targeting of intracellular bacteria by the autophagic machinery, either in the cytoplasm or within vacuolar compartments, helps to control bacterial proliferation in the host cell, controlling also the spreading of the infection. In this review we will describe the means used by diverse bacterial pathogens to survive intracellularly and how they are recognized by the autophagic molecular machinery, as well as the mechanisms used to avoid autophagic clearance. PMID:24137567

  9. Endothelial Progenitor Cell Dysfunction in Polycystic Ovary Syndrome: Implications for The Genesis of Cardiovascular Diseases

    PubMed Central

    Kao, Yu-Hsun; Chiu, Wan-Chun; Hsu, Ming-I; Chen, Yi-Jen

    2013-01-01

    Polycystic ovary syndrome (PCOS), the most common endocrine disorder affecting women of reproductive age, is characterized by hyperandrogenism and insulin resistance. Women with PCOS have a higher risk for cardiovascular diseases (CVDs) and endothelial dysfunction. The mechanisms underlying these risks are unclear. Human peripheral blood contains circulating endothelial progenitor cells (EPCs) derived from bone marrow that have the ability to proliferate and differentiate into mature endothelial cells, which may contribute to vessel homeostasis and repair. PCOS is associated with insulin resistance, hyperinsulinemia, and dyslipidemia, which may result in EPC dysfunction. In this review, we summarize the potential mechanisms of EPC dysfunction in PCOS, which possibly result in a higher genesis of CVDs in PCOS-affected subjects. PMID:24520442

  10. An essential role of the mitochondrial electron transport chain in cell proliferation is to enable aspartate synthesis

    PubMed Central

    Birsoy, Kıvanç; Wang, Tim; Chen, Walter; Freinkman, Elizaveta; Abu-Remaileh, Monther; Sabatini, David M.

    2015-01-01

    Summary The mitochondrial electron transport chain (ETC) enables many metabolic processes, but why its inhibition suppresses cell proliferation is unclear. It is also not well understood why pyruvate supplementation allows cells lacking ETC function to proliferate. We used a CRISPR-based genetic screen to identify genes whose loss sensitizes human cells to phenformin, a complex I inhibitor. The screen yielded GOT1, the cytosolic aspartate aminotransferase, loss of which kills cells upon ETC inhibition. GOT1 normally consumes aspartate to transfer electrons into mitochondria, but, upon ETC inhibition, it reverses to generate aspartate in the cytosol, which partially compensates for the loss of mitochondrial aspartate synthesis. Pyruvate stimulates aspartate synthesis in a GOT1-dependent fashion, which is required for pyruvate to rescue proliferation of cells with ETC dysfunction. Aspartate supplementation or overexpression of an aspartate transporter allows cells without ETC activity to proliferate. Thus, enabling aspartate synthesis is an essential role of the ETC in cell proliferation. PMID:26232224

  11. Experimental Bacterial Endocarditis

    PubMed Central

    Durack, David T.; Beeson, Paul B.

    1972-01-01

    A method has been developed for assessing metabolic activity of bacteria in the vegetations of bacterial endocarditis using a labelled metabolite and autoradiography. Evidence provided by this technique suggests that there are different degrees of activity between superficial and more deeply placed bacterial colonies, and that variations in activity also exist within a single group of organisms. The possible relevance of these findings to the antibiotic therapy of endocarditis is discussed. ImagesFigs. 1-3Figs. 4-5 PMID:4111329

  12. Cerebral protection: inflammation, endothelial dysfunction, and postoperative cognitive dysfunction.

    PubMed

    Riedel, Bernhard; Browne, Kimberley; Silbert, Brendan

    2014-02-01

    Postoperative cognitive dysfunction (POCD) is a well recognized perioperative syndrome, with approximately 15% of patients over the age of 60 years displaying objectively measured decrease in cognitive function as a consequence of anesthesia and surgery. The exact cause, however, remains unknown. This review aims to update anesthesiologists on the recent advancements in the understanding of the pathophysiology of POCD. Recent evidence suggests that the observed predilection to POCD is likely mediated by a neuro-inflammatory response - with surgery being a major contributing factor. The blood-brain barrier, a highly specialized endothelial layer, is exquisitely sensitive to an inflammatory insult and implicated in the cause of other neurocognitive syndromes also characterized by neuro-inflammation such as cerebral malaria. Inflammatory changes may disrupt the blood-brain barrier and facilitate migration of macrophages into the brain, damaging synapses and neurones and ultimately lead to POCD. This review explores the important question of causality - the potential relationship between inflammation, endothelial dysfunction, and postoperative cognitive decline. Recent research points to a central role of a neuro-inflammatory cascade in POCD, with endothelial dysfunction potentially aggravating the insult. Investigating the genomic and molecular mechanisms that underlie the intervariation in the inflammatory response to surgery, improving the identification of appropriate endothelial and inflammatory biomarkers, and developing endothelial modulatory and anti-inflammatory (prevention and resolution) strategies are key areas of future translational research. This is important as the elderly, who show increased susceptibility to this and other perioperative illness syndromes, represent an ever-increasing proportion of patients presenting for surgery.

  13. [The human gut microbiota: Interactions with the host and dysfunctions].

    PubMed

    Lepage, P

    2017-05-12

    The human intestinal microbiota is composed of approximately 100,000 billion microorganisms with the average total number of different commensal bacterial species estimated at over 500 per individual. The human intestinal microbiota can be considered as an organ within another, which co-evolved with its host to achieve a symbiotic relationship leading to physiological homeostasis. The host provides an environment enriched in nutrients and the microbiota provides essential functions. Dysbiosis of the intestinal microbiota (changes in bacterial composition) has been associated with local dysfunctions of the gastrointestinal tract, such as inflammatory bowel disease or irritable bowel syndrome but also with obesity and metabolic diseases. However, a better understanding of the human intestinal ecosystem is still needed to understand the exact role of the microbiota in health and disease. Most intestinal bacteria are anaerobic and therefore, for the large majority, impossible to culture at present. Consequently, their function cannot be inferred from data on their composition. Today, with the help of a metagenomic approach, the bacterial genomic content of an ecosystem and the associated functions can be directly accessed from the environment without culture. Copyright © 2017 SPLF. Published by Elsevier Masson SAS. All rights reserved.

  14. Asthma: vocal cord dysfunction (VCD) and other dysfunctional breathing disorders.

    PubMed

    Balkissoon, Ron; Kenn, Klaus

    2012-12-01

    Vocal cord dysfunction (VCD) and dysfunctional breathing (DB) disorders may mimic or coexist with asthma, leading to overtreatment with corticosteroids with consequent morbidity. Iatrogenic complications can be averted by early and correct diagnosis. VCD, also termed paradoxical vocal fold motion disorder (PVFMD), is characterized by intermittent paradoxical adduction of the vocal cords, mainly during inspiration, leading to airflow obstruction and dyspnea. Patients with VCD may have repetitive emergency room visits due to acute dyspnea (mimicking exacerbations of asthma). In the seminal descriptions of VCD, young women (often with psychiatric issues) predominated; however, other groups at increased risk for developing VCD include elite athletes, military recruits, and individuals exposed to irritants (inhaled or aspirated). Chronic postnasal drip, laryngopharyngeal reflux (LPR), and gastroesophageal reflux (GER) may lead to laryngeal hyperresponsiveness. The diagnosis of VCD may be difficult because physical exam and spirometry may be normal between episodes. During symptomatic episodes, spirometry typically reveals variable extrathoracic airway obstruction (truncated inspiratory flow volume loop). The gold standard for identifying VCD is flexible fiberoptic rhinolaryngoscopy. Management of VCD includes identification and treatment of underlying disorders (eg, chronic postnasal drip, LPR, GER, anxiety, depression) and a multidisciplinary approach (including highly trained speech therapists). Speech therapy and biofeedback play a critical role in teaching techniques to override various dysfunctional breathing habits. When postnasal drip, LPR, or GER coexist, these disorders should be aggressively treated. With successful therapy, corticosteroids can often be discontinued. During severe, acute episodes of VCD, therapeutic strategies include heliox (80% helium/20% oxygen), topical lidocaine, anxiolytics, and superior laryngeal blocks with Clostridium botulinum toxin

  15. [Diagnosis of bacterial vaginosis].

    PubMed

    Djukić, Slobodanka; Ćirković, Ivana; Arsić, Biljana; Garalejić, Eliana

    2013-01-01

    Bacterial vaginosis is a common, complex clinical syndrome characterized by alterations in the normal vaginal flora. When symptomatic, it is associated with a malodorous vaginal discharge and on occasion vaginal burning or itching. Under normal conditions, lactobacilli constitute 95% of the bacteria in the vagina. Bacterial vaginosis is associated with severe reduction or absence of the normal H2O2-producing lactobacilli and overgrowth of anaerobic bacteria and Gardnerella vaginalis, Atopobium vaginae, Mycoplasma hominis and Mobiluncus species. Most types of infectious disease are diagnosed by culture, by isolating an antigen or RNA/DNA from the microbe, or by serodiagnosis to determine the presence of antibodies to the microbe. Therefore, demonstration of the presence of an infectious agent is often a necessary criterion for the diagnosis of the disease. This is not the case for bacterial vaginosis, since the ultimate cause of the disease is not yet known. There are a variety of methods for the diagnosis of bacterial vaginosis but no method can at present be regarded as the best. Diagnosing bacterial vaginosis has long been based on the clinical criteria of Amsel, whereby three of four defined criteria must be satisfied. Nugent's scoring system has been further developed and includes validation of the categories of observable bacteria structures. Up-to-date molecular tests are introduced, and better understanding of vaginal microbiome, a clear definition for bacterial vaginosis, and short-term and long-term fluctuations in vaginal microflora will help to better define molecular tests within the broader clinical context.

  16. Nuclear Proliferation Technology Trends Analysis

    SciTech Connect

    Zentner, Michael D.; Coles, Garill A.; Talbert, Robert J.

    2005-10-04

    A process is underway to develop mature, integrated methodologies to address nonproliferation issues. A variety of methodologies (both qualitative and quantitative) are being considered. All have one thing in common, a need for a consistent set of proliferation related data that can be used as a basis for application. One approach to providing a basis for predicting and evaluating future proliferation events is to understand past proliferation events, that is, the different paths that have actually been taken to acquire or attempt to acquire special nuclear material. In order to provide this information, this report describing previous material acquisition activities (obtained from open source material) has been prepared. This report describes how, based on an evaluation of historical trends in nuclear technology development, conclusions can be reached concerning: (1) The length of time it takes to acquire a technology; (2) The length of time it takes for production of special nuclear material to begin; and (3) The type of approaches taken for acquiring the technology. In addition to examining time constants, the report is intended to provide information that could be used to support the use of the different non-proliferation analysis methodologies. Accordingly, each section includes: (1) Technology description; (2) Technology origin; (3) Basic theory; (4) Important components/materials; (5) Technology development; (6) Technological difficulties involved in use; (7) Changes/improvements in technology; (8) Countries that have used/attempted to use the technology; (9) Technology Information; (10) Acquisition approaches; (11) Time constants for technology development; and (12) Required Concurrent Technologies.

  17. Low Proliferation and Differentiation Capacities of Adult Hippocampal Stem Cells Correlate with Memory Dysfunction in Humans

    ERIC Educational Resources Information Center

    Coras, Roland; Siebzehnrubl, Florian A.; Pauli, Elisabeth; Huttner, Hagen B.; Njunting, Marleisje; Kobow, Katja; Villmann, Carmen; Hahnen, Eric; Neuhuber, Winfried; Weigel, Daniel; Buchfelder, Michael; Stefan, Hermann; Beck, Heinz; Steindler, Dennis A.; Blumcke, Ingmar

    2010-01-01

    The hippocampal dentate gyrus maintains its capacity to generate new neurons throughout life. In animal models, hippocampal neurogenesis is increased by cognitive tasks, and experimental ablation of neurogenesis disrupts specific modalities of learning and memory. In humans, the impact of neurogenesis on cognition remains unclear. Here, we…

  18. Low Proliferation and Differentiation Capacities of Adult Hippocampal Stem Cells Correlate with Memory Dysfunction in Humans

    ERIC Educational Resources Information Center

    Coras, Roland; Siebzehnrubl, Florian A.; Pauli, Elisabeth; Huttner, Hagen B.; Njunting, Marleisje; Kobow, Katja; Villmann, Carmen; Hahnen, Eric; Neuhuber, Winfried; Weigel, Daniel; Buchfelder, Michael; Stefan, Hermann; Beck, Heinz; Steindler, Dennis A.; Blumcke, Ingmar

    2010-01-01

    The hippocampal dentate gyrus maintains its capacity to generate new neurons throughout life. In animal models, hippocampal neurogenesis is increased by cognitive tasks, and experimental ablation of neurogenesis disrupts specific modalities of learning and memory. In humans, the impact of neurogenesis on cognition remains unclear. Here, we…

  19. Pharmacotherapy of Sexual Dysfunctions : Current Status

    PubMed Central

    Avasthi, Ajith; Biswas, Parthasarathy

    2004-01-01

    The sexual dysfunctions are one of the most prevalent conditions. Sexual dysfunctions can have profound effect on the psychological well-being of an individual and the psychosexual relationship of a couple. Management of the sexual dysfunction should be preceded by an accurate diagnosis reached after a complete medical and sexual history and physical examination. Current focus of researchers has been on understanding the pathophysiology of erectile dysfunction, premature ejaculation and other sexual dysfunctions that can help in developing newer pharmacological cures for these conditions. Recently, a number of clinical trials have studied the potential effectiveness of the phosphodiesterase (PDE)-5 inhibitor sildenafil in the treatment of Erectile Dysfunction (ED) and Premature Ejaculation (PME). The introduction of PDE-5 inhibitors like sildenafil, vardenafil and tadalafil has revolutionized the treatment of sexual dysfunctions. This review focuses on the recent pharmacological advances in the treatment of common sexual dysfunctions like ED and PME with special focus on the role of PDE-5 inhibitors. Also discussed is the pharmacological treatment of other less prevalent and recognized disorders like female sexual dysfunction, drug induced sexual dysfunction etc. PMID:21224902

  20. Swallowing dysfunction following endotracheal intubation

    PubMed Central

    Tsai, Min-Hsuan; Ku, Shih-Chi; Wang, Tyng-Guey; Hsiao, Tzu-Yu; Lee, Jang-Jaer; Chan, Ding-Cheng; Huang, Guan-Hua; Chen, Cheryl Chia-Hui

    2016-01-01

    Abstract To evaluate postextubation swallowing dysfunction (PSD) 21 days after endotracheal extubation and to examine whether PSD is time-limited and whether age matters. For this prospective cohort study, we evaluated 151 adult critical care patients (≥20 years) who were intubated for at least 48 hours and had no pre-existing neuromuscular disease or swallowing dysfunction. Participants were assessed for time (days) to pass bedside swallow evaluations (swallow 50 mL of water without difficulty) and to resume total oral intake. Outcomes were compared between younger (20–64 years) and older participants (≥65 years). PSD, defined as inability to swallow 50 mL of water within 48 hours after extubation, affected 92 participants (61.7% of our sample). At 21 days postextubation, 17 participants (15.5%) still failed to resume total oral intake and were feeding-tube dependent. We found that older participants had higher PSD rates at 7, 14, and 21 days postextubation, and took significantly longer to pass the bedside swallow evaluations (5.0 vs 3.0 days; P = 0.006) and to resume total oral intake (5.0 vs 3.0 days; P = 0.003) than their younger counterparts. Older participants also had significantly higher rates of subsequent feeding-tube dependence than younger patients (24.1 vs 5.8%; P = 0.008). Excluding patients with pre-existing neuromuscular dysfunction, PSD is common and prolonged. Age matters in the time needed to recover. Swallowing and oral intake should be monitored and interventions made, if needed, in the first 7 to 14 days postextubation, particularly for older patients. PMID:27310972

  1. Birth weight and ovulatory dysfunction.

    PubMed

    Shayeb, A G; Harrild, K; Bhattacharya, S

    2014-02-01

    To explore the association between birthweight and ovulatory dysfunction in adulthood. Case-control study. Northeast of Scotland University Hospital, hosting the regional fertility centre and maternity unit. A total of 18,846 mother-daughter record pairs from the Aberdeen Fertility Centre Data Set and the Aberdeen Maternity and Neonatal Databank (AMND). Cases were the daughters with ovulatory dysfunction attending the Aberdeen Fertility Centre between 1992 and 2007, Control group 1 included the daughters attending the fertility centre with confirmed ovulation, and Control group 2 included all women naturally fertile who gave birth in Aberdeen during the same period. The electronic maternity records of the mothers of women in the three groups were retrieved from AMND and compared. Daughters' birthweight and standardised birthweight, characteristics of mothers and daughters at delivery and current daughters' characteristics. Cases, Control group 1 and Control group 2 included 466, 548 and 17,832 daughters, respectively. The mean birthweight (standard deviation) in grams was comparable between Cases 3203 (522), Control group 1, 3235 (482) P = 0.30, and Control group 2, 3226 (495) P = 0.31. The proportions of daughters born small for gestational age, large for gestational age, or preterm were comparable between the Cases group and each Control group, as was the mode of delivery and Apgar scores at 1 and 5 minutes. The age at delivery, body mass index, social class or pregnancy complications were comparable in the mothers of the Cases and each Control group. Ovulatory dysfunction does not appear to be related to birthweight or perinatal events. © 2013 RCOG.

  2. Vaccination-related shoulder dysfunction.

    PubMed

    Bodor, Marko; Montalvo, Enoch

    2007-01-08

    We present two cases of shoulder pain and weakness following influenza and pneumococcal vaccine injections provided high into the deltoid muscle. Based on ultrasound measurements, we hypothesize that vaccine injected into the subdeltoid bursa caused a periarticular inflammatory response, subacromial bursitis, bicipital tendonitis and adhesive capsulitis. Resolution of symptoms followed corticosteroid injections to the subacromial space, bicipital tendon sheath and glenohumeral joint, followed by physical therapy. We conclude that the upper third of the deltoid muscle should not be used for vaccine injections, and the diagnosis of vaccination-related shoulder dysfunction should be considered in patients presenting with shoulder pain following a vaccination.

  3. Vocal cord dysfunction during wartime.

    PubMed

    Craig, T; Sitz, K; Squire, E; Smith, L; Carpenter, G

    1992-11-01

    Vocal cord dysfunction (VCD) often masquerades as asthma. The diagnosis is rarely suspected, but should be considered in cases of asthma that present atypically or that fail to respond to standard therapy. The frequency of VCD would be expected to increase during times of stress, including periods of war, since it is thought to be a conversion reaction. A high level of suspicion for VCD is essential to make the diagnosis so as to avoid unnecessary, potentially toxic medications and to direct the patient to prompt psychiatric care, which along with speech therapy, is the cornerstone of care.

  4. Cerebrovascular Dysfunction in Preeclamptic Pregnancies

    PubMed Central

    Hammer, Erica S.; Cipolla, Marilyn J.

    2016-01-01

    Preeclampsia is a hypertensive, multi-system disorder of pregnancy that affects several organ systems, including the maternal brain. Cerebrovascular dysfunction during preeclampsia can lead to cerebral edema, seizures, stroke and potentially maternal mortality. This review will discuss the effects of preeclampsia on the cerebrovasculature that may adversely affect the maternal brain, including cerebral blood flow (CBF) autoregulation and blood-brain barrier disruption, and the resultant clinical outcomes including posterior reversible encephalopathy syndrome (PRES) and maternal stroke. Potential long-term cognitive outcomes of preeclampsia and the role of the cerebrovasculature are also reviewed. PMID:26126779

  5. Male sexual dysfunction in Asia.

    PubMed

    Ho, Christopher Ck; Singam, Praveen; Hong, Goh Eng; Zainuddin, Zulkifli Md

    2011-07-01

    Sex has always been a taboo subject in Asian society. However, over the past few years, awareness in the field of men's sexual health has improved, and interest in sexual health research has recently increased. The epidemiology and prevalence of erectile dysfunction, hypogonadism and premature ejaculation in Asia are similar in the West. However, several issues are specific to Asian males, including culture and beliefs, awareness, compliance and the availability of traditional/complementary medicine. In Asia, sexual medicine is still in its infancy, and a concerted effort from the government, relevant societies, physicians and the media is required to propel sexual medicine to the forefront of health care.

  6. Nonpharmacologic Treatment of Erectile Dysfunction

    PubMed Central

    Montague, Drogo K

    2002-01-01

    Nonpharmacologic treatment for erectile dysfunction (ED) includes sex therapy, the use of vacuum erection devices, penile prosthesis implantation, and penile vascular surgery. Sex therapy is indicated for psychogenic ED and is at times a useful adjunct for other treatments in men with mixed psychogenic and organic ED. Vacuum erection devices produce usable erections in over 90% of patients; however, patient and partner acceptability is an issue. Three-piece inflatable penile prostheses create flaccidity and an erection that comes close to that which occurs naturally. Penile vascular surgery has shown greatest efficacy in young men with vasculogenic ED resulting from pelvic or perineal trauma. PMID:16986016

  7. Angelman syndrome and thyroid dysfunction.

    PubMed

    Monterrubio-Ledezma, C E; Bobadilla-Morales, L; Pimentel-Gutiérrez, H J; Corona-Rivera, J R; Corona-Rivera, A

    2012-01-01

    Angelman syndrome (AS) is a neurogenetic syndrome, has a prevalence of 1:10,000 to 1:40,000. Patients with AS have genetic alterations in maternal imprinting gene UB3A (15q11-q13) and molecular evaluations confirm the diagnosis. Our aim is to report a new case with AS and subclinical hypothyroidism (SCH) without goiter. Thyroid dysfunction has not been described as part of alterations in AS; the exact pathogenic mechanisms of SCH in patients with AS remains incompletely unknown.

  8. Drug addiction and sexual dysfunction.

    PubMed

    Zaazaa, Adham; Bella, Anthony J; Shamloul, Rany

    2013-09-01

    This article attempts to review the most current and the well-established facts concerning drug addiction and sexual dysfunction. Surprisingly, even though alcohol is prevalent in many societies with many myths surrounding its sexual-enhancing effects, current scientific research cannot provide a solid conclusion on its effect on sexual function. Unfortunately, the same concept applies to tobacco smoking; however, most of the current knowledge tends to support the notion that it, indeed, can negatively affect sexual function. Similar ambiguities also prevail with substances of abuse.

  9. [Handedness, cerebral dysfunction and dyslexia].

    PubMed

    Céspedes, A; Berneosolo, J; Bravo, L; Pinto, A

    1989-01-01

    A frequency distribution of handedness and its relations with minor signs of neurological dysfunction was studied in a group of 56 dyslexic children and 56 good readers. An unusual frequency of 18% left-handed children in the dyslexic group and the high frequency of soft signs in this lefthanded children, is in concordance with recent hypothesis about the dysgenesic brain origin of dyslexia and lefthandedness, postulated by Galaburda, Geschwind and others. They suggest a distorted cortical development of the brain areas related with linguistic functions, with subsequent expression on verbal language reading ability and handedness.

  10. Male sexual dysfunction in Asia

    PubMed Central

    Ho, Christopher CK; Singam, Praveen; Hong, Goh Eng; Zainuddin, Zulkifli Md

    2011-01-01

    Sex has always been a taboo subject in Asian society. However, over the past few years, awareness in the field of men's sexual health has improved, and interest in sexual health research has recently increased. The epidemiology and prevalence of erectile dysfunction, hypogonadism and premature ejaculation in Asia are similar in the West. However, several issues are specific to Asian males, including culture and beliefs, awareness, compliance and the availability of traditional/complementary medicine. In Asia, sexual medicine is still in its infancy, and a concerted effort from the government, relevant societies, physicians and the media is required to propel sexual medicine to the forefront of health care. PMID:21643001

  11. Mitochondrial dysfunctions in Parkinson's disease.

    PubMed

    Gautier, C A; Corti, O; Brice, A

    2014-05-01

    Neurodegenerative disorders (ND) include a wide spectrum of diseases characterized by progressive neuronal dysfunctions or degeneration. With an estimated cost of 135 billion € in 2010 in the European Union (Olesen et al., 2012), they put an enormous economic as well as social burden on modern societies. Hence, they have been the subject of a huge amount of research for the last fifty years. For many of these diseases, our understanding of their profound causes is incomplete and this hinders the discovery of efficient therapies. ND form a highly heterogeneous group of diseases affecting various neuronal subpopulations reflecting different origins and different pathological mechanisms. However, some common themes in the physiopathology of these disorders are emerging. There is growing evidence that mitochondrial dysfunctions play a pivotal role at some point in the course of neurodegeneration. In some cases (e.g. Alzheimer's disease, amyotrophic lateral sclerosis), impairment of mitochondrial functions probably occurs late in the course of the disease. In a subset of ND, current evidence suggests that mitochondrial dysfunctions play a more seminal role in neuronal demise. Parkinson's disease (PD) presents one of the strongest cases based in part on post-mortem studies that have shown mitochondrial impairment (e.g. reduced complex I activity) and oxidative damage in idiopathic PD brains. The occurrence of PD is largely sporadic, but clinical syndromes resembling sporadic PD have been linked to specific environmental insults or to mutations in at least 5 distinct genes (α-synuclein, parkin, DJ-1, PINK1 and LRRK2). It is postulated that the elucidation of the pathogenic mechanisms underlying the selective dopaminergic degeneration in familial and environmental Parkinsonism should provide important clues to the pathogenic mechanisms responsible for idiopathic PD. Hence, numerous cellular and animal models of the disease have been generated that mimic these

  12. Bacterial Cell Mechanics.

    PubMed

    Auer, George K; Weibel, Douglas B

    2017-07-25

    Cellular mechanical properties play an integral role in bacterial survival and adaptation. Historically, the bacterial cell wall and, in particular, the layer of polymeric material called the peptidoglycan were the elements to which cell mechanics could be primarily attributed. Disrupting the biochemical machinery that assembles the peptidoglycan (e.g., using the β-lactam family of antibiotics) alters the structure of this material, leads to mechanical defects, and results in cell lysis. Decades after the discovery of peptidoglycan-synthesizing enzymes, the mechanisms that underlie their positioning and regulation are still not entirely understood. In addition, recent evidence suggests a diverse group of other biochemical elements influence bacterial cell mechanics, may be regulated by new cellular mechanisms, and may be triggered in different environmental contexts to enable cell adaptation and survival. This review summarizes the contributions that different biomolecular components of the cell wall (e.g., lipopolysaccharides, wall and lipoteichoic acids, lipid bilayers, peptidoglycan, and proteins) make to Gram-negative and Gram-positive bacterial cell mechanics. We discuss the contribution of individual proteins and macromolecular complexes in cell mechanics and the tools that make it possible to quantitatively decipher the biochemical machinery that contributes to bacterial cell mechanics. Advances in this area may provide insight into new biology and influence the development of antibacterial chemotherapies.

  13. Autonomic dysfunction, immune regulation, and multiple sclerosis.

    PubMed

    Racosta, Juan Manuel; Kimpinski, Kurt

    2016-02-01

    To review existing evidence regarding interactions between the autonomic nervous system and the immune system functions in multiple sclerosis. We reviewed the literature regarding new insights linking autonomic dysfunction to immune deregulation in multiple sclerosis, with particular focus on the specific influence of sympathetic and parasympathetic dysfunction on inflammatory and neurodegenerative processes. Autonomic dysfunction is common in multiple sclerosis, representing a significant cause of disability. Several connections between pathologic immune pathways and the autonomic nervous system function were found. Autonomic dysfunction may enhance inflammatory and neurodegenerative pathways that are of major importance in multiple sclerosis. Autonomic dysfunction can present with highly variable manifestations. Sympathetic and parasympathetic dysfunction displays different patterns in multiple sclerosis, with specific impact on inflammation and neurodegeneration.

  14. Bacteroides uniformis CECT 7771 Ameliorates Metabolic and Immunological Dysfunction in Mice with High-Fat-Diet Induced Obesity

    PubMed Central

    Gauffin Cano, Paola; Santacruz, Arlette; Moya, Ángela; Sanz, Yolanda

    2012-01-01

    Background Associations have been made between obesity and reduced intestinal numbers of members of the phylum Bacteroidetes, but there is no direct evidence of the role these bacteria play in obesity. Herein, the effects of Bacteroides uniformis CECT 7771 on obesity-related metabolic and immune alterations have been evaluated. Methods and Findings Adult (6–8 week) male wild-type C57BL-6 mice were fed a standard diet or a high-fat-diet HFD to induce obesity, supplemented or not with B. uniformis CECT 7771 for seven weeks. Animal weight was monitored and histologic, biochemical, immunocompetent cell functions, and features of the faecal microbiota were analysed after intervention. The oral administration of B. uniformis CECT 7771 reduced body weight gain, liver steatosis and liver cholesterol and triglyceride concentrations and increased small adipocyte numbers in HFD-fed mice. The strain also reduced serum cholesterol, triglyceride, glucose, insulin and leptin levels, and improved oral tolerance to glucose in HFD fed mice. The bacterial strain also reduced dietary fat absorption, as indicated by the reduced number of fat micelles detected in enterocytes. Moreover, B. uniformis CECT 7771 improved immune defence mechanisms, impaired in obesity. HFD-induced obesity led to a decrease in TNF-α production by peritoneal macrophages stimulated with LPS, conversely, the administration of B. uniformis CECT 7771 increased TNF-α production and phagocytosis. Administering this strain also increased TNF-α production by dendritic cells (DCs) in response to LPS stimulation, which was significantly reduced by HFD. B. uniformis CECT 7771 also restored the capacity of DCs to induce a T-cell proliferation response, which was impaired in obese mice. HFD induced marked changes in gut microbiota composition, which were partially restored by the intervention. Conclusions Altogether, the findings indicate that administration of B. uniformis CECT 7771 ameliorates HFD-induced metabolic

  15. Orgasmic Dysfunction after Radical Prostatectomy

    PubMed Central

    Ventimiglia, Eugenio; Cazzaniga, Walter; Montorsi, Francesco; Salonia, Andrea

    2017-01-01

    In addition to urinary incontinence and erectile dysfunction, several other impairments of sexual function potentially occurring after radical prostatectomy (RP) have been described; as a whole, these less frequently assessed disorders are referred to as neglected side effects. In particular, orgasmic dysfunctions (ODs) have been reported in a non-negligible number of cases, with detrimental impacts on patients' overall sexual life. This review aimed to comprehensively discuss the prevalence and physiopathology of post-RP ODs, as well as potential treatment options. Orgasm-associated incontinence (climacturia) has been reported to occur in between 20% and 93% of patients after RP. Similarly, up to 19% of patients complain of postoperative orgasm-associated pain, mainly referred pain at the level of the penis. Moreover, impairment in the sensation of orgasm or even complete anorgasmia has been reported in 33% to 77% of patients after surgery. Clinical and surgical factors including age, the use of a nerve-sparing technique, and robotic surgery have been variably associated with the risk of ODs after RP, although robust and reliable data allowing for a proper estimation of the risk of postoperative orgasmic function impairment are still lacking. Likewise, little evidence regarding the management of postoperative ODs is currently available. In general, physicians should be aware of the prevalence of ODs after RP, in order to properly counsel all patients both preoperatively and immediately post-RP about the potential occurrence of bothersome and distressful changes in their overall sexual function. PMID:28459142

  16. [Diaphragm dysfunction : Facts for clinicians].

    PubMed

    Bruells, C S; Marx, G

    2016-10-20

    Diaphragm function is crucial for patient outcome in the ICU setting and during the treatment period. The occurrence of an insufficiency of the respiratory pump, which is predominantly formed by the diaphragm, may result in intubation after failure of noninvasive ventilation. Especially patients suffering from chronic obstructive pulmonary disease are in danger of hypercapnic respiratory failure. Changes in biomechanical properties and fiber texture of the diaphragm are further cofactors directly leading to a need for intubation and mechanical ventilation. After intubation and the following inactivity the diaphragm is subject to profound pathophysiologic changes resulting in atrophy and dysfunction. Besides this inactivity-triggered mechanism (termed as ventilator-induced diaphragmatic dysfunction) multiple factors, comorbidities, pharmaceutical agents and additional hits during the ICU treatment, especially the occurrence of sepsis, influence diaphragm homeostasis and can lead to weaning failure. During the weaning process monitoring of diaphragm function can be done with invasive methods - ultrasound is increasingly established to monitor diaphragm contraction, but further and better powered studies are in need to prove its value as a diagnostic tool.

  17. [Male sexual dysfunctions and homosexuality].

    PubMed

    Leuillet, P; Cour, F; Droupy, S

    2013-07-01

    The homosexuality, which expresses itself through a varied and complex behavior that those whom are shared by the heterosexual majority, is not that a simple sexual behavior, obvious or not, but a whole set of attitudes, affects, preferences, values, lifestyle which concern profoundly the individual, as the heterosexuality. A review of the literature using PubMed database has been performed to select 38 articles. Among sexual difficulties met by the gays, erectile dysfunction and hypoactive sexual desire are the more frequent. Concerning the ejaculation disorders observed in the gay population, premature ejaculation is rather rare in comparison with heterosexual men; however delayed ejaculation or anejaculation are more frequent. Painful sexual disorders in particular anodyspareunia are also reported. Sexual disorder management must follows the classic rules but it is necessary to be aware how to approach the specific questions affecting the homosexual persons. Still the homosexual person has to find a competent therapist, "opened" to the sexual problem of the homosexuals, with the aim of a care privileging the efficiency to efficacy in the respect for the truth of the homosexual person. The homosexuality is the only one of the "unusual" sexual conducts to possibly concern the daily medical practice due to is prevalence. The management of sexual dysfunctions must privilege the "meeting" in a quest of sense in front of any sexual symptom, whatever the individual sexual orientation. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  18. Insulin Resistance and Mitochondrial Dysfunction.

    PubMed

    Gonzalez-Franquesa, Alba; Patti, Mary-Elizabeth

    2017-01-01

    Insulin resistance precedes and predicts the onset of type 2 diabetes (T2D) in susceptible humans, underscoring its important role in the complex pathogenesis of this disease. Insulin resistance contributes to multiple tissue defects characteristic of T2D, including reduced insulin-stimulated glucose uptake in insulin-sensitive tissues, increased hepatic glucose production, increased lipolysis in adipose tissue, and altered insulin secretion. Studies of individuals with insulin resistance, both with established T2D and high-risk individuals, have consistently demonstrated a diverse array of defects in mitochondrial function (i.e., bioenergetics, biogenesis and dynamics). However, it remains uncertain whether mitochondrial dysfunction is primary (critical initiating defect) or secondary to the subtle derangements in glucose metabolism, insulin resistance, and defective insulin secretion present early in the course of disease development. In this chapter, we will present the evidence linking mitochondrial dysfunction and insulin resistance, and review the potential for mitochondrial targets as a therapeutic approach for T2D.

  19. [Oxidative stress and endothelial dysfunction].

    PubMed

    Jarasūniene, Dalia; Simaitis, Audrius

    2003-01-01

    Growing numbers of morbidity and mortality due to the Coronary Heart Disease (CHD) is recognized as the more increasing challenge in the world. The initial stage of atherosclerosis, early diagnosis and treatment of CHD are the main objectives of current research. Endothelium dysfunction, the earliest expression of the atherosclerotic process is associated with subtle biochemical changes that gradually are transformed into the structural changes of the arterial wall. The theory of free radicals is the most common among the atherosclerosis explanations. Overproduction or impaired neutralization of the free radicals accounts for oxidative stress that is causing substantial damage to the low density lipoproteins, nitric oxyde (NO), endothelium cells, tissue cells and finally leads to the endothelium dysfuction. Pathophysiology of oxidative stress and its role in the endothelium dysfunction are discussed in this paper. Positive role of various medications (statins, angiotensin converting enzym inhibitors, aldosteron antagonists, estrogens, antioxidants, b-blockers with vasodilatative properties) to the oxidative stress and consequently to the endothelium dysfuction are discussed as well.

  20. Significance of feeding dysfunction in eosinophilic esophagitis.

    PubMed

    Menard-Katcher, Calies; Henry, Michelle; Furuta, Glenn T; Atkins, Dan; Maune, Nancy Creskoff; Haas, Angela M

    2014-08-21

    Feeding dysfunction is a frequent presenting symptom of eosinophilic esophagitis (EoE). Here we present 3 children of various ages whose manifestations of EoE associated feeding dysfunction led to significant and life altering impact on their growth and development. Early identification of presenting symptoms of EoE will allow for prompt diagnosis and initiation of appropriate treatments. Recognition of salient features of dysfunction and treatment by feeding therapists and nutritionists led to symptom resolution and growth.

  1. Proliferation Vulnerability Red Team report

    SciTech Connect

    Hinton, J.P.; Barnard, R.W.; Bennett, D.E.

    1996-10-01

    This report is the product of a four-month independent technical assessment of potential proliferation vulnerabilities associated with the plutonium disposition alternatives currently under review by DOE/MD. The scope of this MD-chartered/Sandia-led study was limited to technical considerations that could reduce proliferation resistance during various stages of the disposition processes below the Stored Weapon/Spent Fuel standards. Both overt and covert threats from host nation and unauthorized parties were considered. The results of this study will be integrated with complementary work by others into an overall Nonproliferation and Arms Control Assessment in support of a Secretarial Record of Decision later this year for disposition of surplus U.S. weapons plutonium.

  2. Lipoproteins of Bacterial Pathogens▿

    PubMed Central

    Kovacs-Simon, A.; Titball, R. W.; Michell, S. L.

    2011-01-01

    Bacterial lipoproteins are a set of membrane proteins with many different functions. Due to this broad-ranging functionality, these proteins have a considerable significance in many phenomena, from cellular physiology through cell division and virulence. Here we give a general overview of lipoprotein biogenesis and highlight examples of the roles of lipoproteins in bacterial disease caused by a selection of medically relevant Gram-negative and Gram-positive pathogens: Mycobacterium tuberculosis, Streptococcus pneumoniae, Borrelia burgdorferi, and Neisseria meningitidis. Lipoproteins have been shown to play key roles in adhesion to host cells, modulation of inflammatory processes, and translocation of virulence factors into host cells. As such, a number of lipoproteins have been shown to be potential vaccines. This review provides a summary of some of the reported roles of lipoproteins and of how this knowledge has been exploited in some cases for the generation of novel countermeasures to bacterial diseases. PMID:20974828

  3. Considerations on bacterial nucleoids.

    PubMed

    Feijoo-Siota, Lucía; Rama, José Luis R; Sánchez-Pérez, Angeles; Villa, Tomás G

    2017-07-01

    The classic genome organization of the bacterial chromosome is normally envisaged with all its genetic markers linked, thus forming a closed genetic circle of duplex stranded DNA (dsDNA) and several proteins in what it is called as "the bacterial nucleoid." This structure may be more or less corrugated depending on the physiological state of the bacterium (i.e., resting state or active growth) and is not surrounded by a double membrane as in eukayotic cells. The universality of the closed circle model in bacteria is however slowly changing, as new data emerge in different bacterial groups such as in Planctomycetes and related microorganisms, species of Borrelia, Streptomyces, Agrobacterium, or Phytoplasma. In these and possibly other microorganisms, the existence of complex formations of intracellular membranes or linear chromosomes is typical; all of these situations contributing to weakening the current cellular organization paradigm, i.e., prokaryotic vs eukaryotic cells.

  4. The relationship between depression and erectile dysfunction.

    PubMed

    Seidman, S N; Roose, S P

    2000-06-01

    Normal sexual function is a biopsychosocial process; sexual dysfunction almost always has organic and psychologic components, and it requires multidisciplinary, goal-directed evaluation and treatment. Factors such as aging, declining testosterone levels, medical illness, certain medications, and comorbid depressive illness can contribute to sexual dysfunction. Erectile dysfunction (ED) is the most common male sexual dysfunction encountered in the clinical setting. Comorbidity between ED and depressive illness is high, but the causal relationship is unclear, and likely bidirectional. In this article, we review the existing literature on the relationship between depression and ED.

  5. Diabetes and sexual dysfunction: current perspectives

    PubMed Central

    Maiorino, Maria Ida; Bellastella, Giuseppe; Esposito, Katherine

    2014-01-01

    Diabetes mellitus is one of the most common chronic diseases in nearly all countries. It has been associated with sexual dysfunction, both in males and in females. Diabetes is an established risk factor for sexual dysfunction in men, as a threefold increased risk of erectile dysfunction was documented in diabetic men, as compared with nondiabetic men. Among women, evidence regarding the association between diabetes and sexual dysfunction are less conclusive, although most studies have reported a higher prevalence of female sexual dysfunction in diabetic women as compared with nondiabetic women. Female sexual function appears to be more related to social and psychological components than to the physiological consequence of diabetes. Hyperglycemia, which is a main determinant of vascular and microvascular diabetic complications, may participate in the pathogenetic mechanisms of sexual dysfunction in diabetes. Moreover, diabetic people may present several clinical conditions, including hypertension, overweight and obesity, metabolic syndrome, cigarette smoking, and atherogenic dyslipidemia, which are themselves risk factors for sexual dysfunction, both in men and in women. The adoption of healthy lifestyles may reduce insulin resistance, endothelial dysfunction, and oxidative stress – all of which are desirable achievements in diabetic patients. Improved well-being may further contribute to reduce and prevent sexual dysfunction in both sexes. PMID:24623985

  6. Erectile dysfunction and coronary heart disease.

    PubMed

    Katsiki, Niki; Wierzbicki, Anthony S; Mikhailidis, Dimitri P

    2015-07-01

    This narrative review discusses the associations of erectile dysfunction with coronary heart disease (CHD) morbidity and mortality, all-cause death and CHD risk factors. Treatment strategies for erectile dysfunction are also mentioned. Erectile dysfunction shares common pathways and risk factors with vascular diseases. Erectile dysfunction has been reported to independently predict CHD events, thus highlighting its role as a marker of early atherosclerosis. Erectile dysfunction prevalence may be followed by the presentation of CHD symptoms in 2-3 years, and a CHD event may occur in 3-5 years. Furthermore, erectile dysfunction has been associated with stroke, peripheral artery disease, diabetes and chronic kidney disease as well as with several CHD risk factors including hypertension, dyslipidaemia, smoking, obesity, metabolic syndrome, hyperuricaemia, arterial stiffness and obstructive sleep apnea syndrome. On the basis of these data, erectile dysfunction may be regarded as a part of polyvascular disease. Patients with erectile dysfunction are at an increased risk for CHD morbidity and/or mortality as well as for all-cause death. Clinicians should monitor patients with erectile dysfunction by assessing their vascular risk and preventing or adequately treating CHD risk factors. In this context, lifestyle interventions should be recommended in addition to drug treatment to attain better outcomes.

  7. Intestinal dysfunction associated with acute thoracolumbar fractures.

    PubMed

    Peschiera, J L; Beerman, S P

    1990-03-01

    The frequency of intestinal dysfunction, particularly intestinal ileus, among patients with acute thoracolumbar fractures and no neurologic compromise was assessed. We reviewed the medical records of 70 patients who met specific criteria. Only four (6%) of these patients developed intestinal dysfunction, manifested by vomiting, abdominal distention, diminished bowel sounds, or an intestinal ileus documented by an abdominal roentgenogram. Conservative initial nutritional management of the patients did not reduce the incidence of intestinal dysfunction. This study suggests that patients with acute thoracolumbar fractures and no neurologic compromise are not at substantial risk of intestinal dysfunction and that nasogastric suction and restriction of oral intake are unnecessary in the initial management of these patients.

  8. Platelets: cell proliferation and atherosclerosis.

    PubMed

    Ross, R

    1979-04-01

    Intimal smooth muscle proliferation is the hallmark of the lesions of atherosclerosis. Endothelial injury is postulated to precede this intimal smooth muscle proliferative response, which is mediated by a potent mitogenic factor derived from adherence, aggregation, and release by platelets at sites of endothelial injury. Smooth muscle proliferation is accompanied by varying amounts of connective tissue formation and intracellular and extracellular lipid deposition, dependent upon the risk factors encountered in each patient. The platelet-derived mitogen (PF) is a stable, cationic, relatively low molecular weight (10,000-30,000) protein that has been partially purified by ion exchange chromotography and gel filtration. Less than 100 ng of PF/ml culture medium can stimulate sparse 3T3 cells or smooth muscle cells, but not endothelial cells, to undergo multiple cell divisions in the presence of 5% cell-free, plasma-derived serum. The latter contains no mitogenic activity. The interaction of the platelet mitogen and plasma-derived components, including lipoproteins, plays a critical role in smooth muscle proliferation in vitro and in vivo in the induction of the lesions of atherosclerosis.

  9. Proliferation and the former Soviet Union

    SciTech Connect

    Not Available

    1994-09-01

    The report examines the whole range of consequences for proliferation of weapons of mass destruction of the Soviet Union's breakup and describes how U.S. assistance may reduce specific proliferation risks in the former Soviet Union.

  10. Mechanisms of endothelial dysfunction: clinical significance and preventive non-pharmacological therapeutic strategies.

    PubMed

    Taddei, S; Ghiadoni, L; Virdis, A; Versari, D; Salvetti, A

    2003-01-01

    Endothelium-derived NO is not only a potent vasodilator but also inhibits platelet aggregation, vascular smooth muscle cell migration and proliferation, monocyte adhesion and adhesion molecule expression, thus protecting the vessel wall against the development of atherosclerosis. Cardiovascular risk factors are associated with an imbalance of the redox equilibrium towards oxidative stress and, therefore, impair the integrity of the endothelium, leading to endothelial activation which involves blunted endothelium-dependent vasodilation (vasodilator dysfunction) as well as inflammatory processes extending to the milieu within the whole vasculature, making plaques prone to rupture. In prospective studies endothelial dysfunction is associated with increased incidence of cardiovascular events. Thus, the prevention of endothelial dysfunction can determine a strong advantage in the clinical outcome of patients with cardiovascular risk factors. Several non-pharmacological interventions can prevent endothelial dysfunction or improve impaired endothelium-dependent vasodilation. Probably the most effective non-pharmacological measure is represented by aerobic physical activity, which can reduce production of oxidative stress associated to increasing age. Moreover, physical activity can improve endothelial dysfunction even in patients with cardiovascular risk factors such as essential hypertension. In addition several other approaches, including vitamin and fish oil supplementation, or tea and red wine consumption, can lead to an improvement of endothelium-dependent vasodilation, possibly by a restoration of NO availability. It is worth noting that most of non-pharmacological measures act by preventing or reducing oxidative stress.

  11. Calibrating bacterial evolution

    PubMed Central

    Ochman, Howard; Elwyn, Susannah; Moran, Nancy A.

    1999-01-01

    Attempts to calibrate bacterial evolution have relied on the assumption that rates of molecular sequence divergence in bacteria are similar to those of higher eukaryotes, or to those of the few bacterial taxa for which ancestors can be reliably dated from ecological or geological evidence. Despite similarities in the substitution rates estimated for some lineages, comparisons of the relative rates of evolution at different classes of nucleotide sites indicate no basis for their universal application to all bacteria. However, there is evidence that bacteria have a constant genome-wide mutation rate on an evolutionary time scale but that this rate differs dramatically from the rate estimated by experimental methods. PMID:10535975

  12. Bacterial transfer RNAs

    PubMed Central

    Shepherd, Jennifer; Ibba, Michael

    2015-01-01

    Transfer RNA is an essential adapter molecule that is found across all three domains of life. The primary role of transfer RNA resides in its critical involvement in the accurate translation of messenger RNA codons during protein synthesis and, therefore, ultimately in the determination of cellular gene expression. This review aims to bring together the results of intensive investigations into the synthesis, maturation, modification, aminoacylation, editing and recycling of bacterial transfer RNAs. Codon recognition at the ribosome as well as the ever-increasing number of alternative roles for transfer RNA outside of translation will be discussed in the specific context of bacterial cells. PMID:25796611

  13. Cyclin C stimulates β-cell proliferation in rat and human pancreatic β-cells

    PubMed Central

    Jiménez-Palomares, Margarita; López-Acosta, José Francisco; Villa-Pérez, Pablo; Moreno-Amador, José Luis; Muñoz-Barrera, Jennifer; Fernández-Luis, Sara; Heras-Pozas, Blanca; Perdomo, Germán; Bernal-Mizrachi, Ernesto

    2015-01-01

    Activation of pancreatic β-cell proliferation has been proposed as an approach to replace reduced functional β-cell mass in diabetes. Quiescent fibroblasts exit from G0 (quiescence) to G1 through pRb phosphorylation mediated by cyclin C/cdk3 complexes. Overexpression of cyclin D1, D2, D3, or cyclin E induces pancreatic β-cell proliferation. We hypothesized that cyclin C overexpression would induce β-cell proliferation through G0 exit, thus being a potential therapeutic target to recover functional β-cell mass. We used isolated rat and human islets transduced with adenovirus expressing cyclin C. We measured multiple markers of proliferation: [3H]thymidine incorporation, BrdU incorporation and staining, and Ki67 staining. Furthermore, we detected β-cell death by TUNEL, β-cell differentiation by RT-PCR, and β-cell function by glucose-stimulated insulin secretion. Interestingly, we have found that cyclin C increases rat and human β-cell proliferation. This augmented proliferation did not induce β-cell death, dedifferentiation, or dysfunction in rat or human islets. Our results indicate that cyclin C is a potential target for inducing β-cell regeneration. PMID:25564474

  14. Hyperthyroidism causes cardiac dysfunction by mitochondrial impairment and energy depletion.

    PubMed

    Maity, Sangeeta; Kar, Dipak; De, Kakali; Chander, Vivek; Bandyopadhyay, Arun

    2013-05-01

    This study elucidates the role of metabolic remodeling in cardiac dysfunction induced by hyperthyroidism. Cardiac hypertrophy, structural remodeling, and expression of the genes associated with fatty acid metabolism were examined in rats treated with triiodothyronine (T3) alone (8 μg/100 g body weight (BW), i.p.) for 15 days or along with a peroxisome proliferator-activated receptor alpha agonist bezafibrate (Bzf; 30 μg/100 g BW, oral) and were found to improve in the Bzf co-treated condition. Ultrastructure of mitochondria was damaged in T3-treated rat heart, which was prevented by Bzf co-administration. Hyperthyroidism-induced oxidative stress, reduction in cytochrome c oxidase activity, and myocardial ATP concentration were also significantly checked by Bzf. Heart function studied at different time points during the course of T3 treatment shows an initial improvement and then a gradual but progressive decline with time, which is prevented by Bzf co-treatment. In summary, the results demonstrate that hyperthyroidism inflicts structural and functional damage to mitochondria, leading to energy depletion and cardiac dysfunction.

  15. Eldecalcitol prevents endothelial dysfunction in postmenopausal osteoporosis model rats.

    PubMed

    Serizawa, Kenichi; Yogo, Kenji; Tashiro, Yoshihito; Takeda, Satoshi; Kawasaki, Ryohei; Aizawa, Ken; Endo, Koichi

    2016-02-01

    Postmenopausal women have high incidence of cardiovascular events as estrogen deficiency can cause endothelial dysfunction. Vitamin D is reported to be beneficial on endothelial function, but it remains controversial whether vitamin D is effective for endothelial dysfunction under the treatment for osteoporosis in postmenopausal women. The aim of this study was to evaluate the endothelial protective effect of eldecalcitol (ELD) in ovariectomized (OVX) rats. ELD (20  ng/kg) was orally administrated five times a week for 4 weeks from 1 day after surgery. After that, flow-mediated dilation (FMD) as an indicator of endothelial function was measured by high-resolution ultrasound in the femoral artery of living rats. ELD ameliorated the reduction of FMD in OVX rats. ELD inhibited the increase in NOX4, nitrotyrosine, and p65 and the decrease in dimer/monomer ratio of nitric oxide synthase in OVX rat femoral arteries. ELD also prevented the decrease in peroxisome proliferator-activated receptor gamma (PPARγ) in femoral arteries and cultured endothelial cells. Although PPARγ is known to inhibit osteoblastogenesis, ELD understandably increased bone mineral density of OVX rats without increase in PPARγ in bone marrow. These results suggest that ELD prevented the deterioration of endothelial function under condition of preventing bone loss in OVX rats. This endothelial protective effect of ELD might be exerted through improvement of endothelial nitric oxide synthase uncoupling, which is mediated by an antioxidative effect through normalization of vascular PPARγ/NF-κB signaling.

  16. A mouse model of urofacial syndrome with dysfunctional urination

    PubMed Central

    Guo, Chunming; Kaneko, Satoshi; Sun, Ye; Huang, Yichen; Vlodavsky, Israel; Li, Xiaokun; Li, Zhong-Rong; Li, Xue

    2015-01-01

    Urofacial syndrome (UFS) is an autosomal recessive disease with severe dysfunctional urination including urinary incontinence (UI). Biallelic mutations of HPSE2 are discovered from UFS patients, suggesting that HPSE2 is a candidate disease gene. Here, we show that deletion of Hpse2 is sufficient to cause the UFS-like phenotype in mice. Hpse2 knockout mutants display a distended bladder (megacystis) phenotype and abnormal voiding behavior similar to that found in patients. While Hpse2 is largely dispensable for detrusor smooth muscle and urothelial cell fate determination, the mutants have significantly lower rates of cell proliferation than wild-type littermate controls. All Hpse2 mutants have a growth retardation phenotype and die within a month after birth. Comprehensive blood chemistry and urinalysis indicate that Hpse2 mutants have renal dysfunction and malnutrition. We provide evidence that transforming growth factor beta (Tgfβ) signaling is attenuated at birth. However, Tgfβ activity is significantly enhanced at later stages when the urological phenotype is severe, and the mutant bladders have accumulated excessive amount of fibrotic tissue. Together, these findings strongly suggest that Hpse2 is a causative gene of human UFS and further uncover unexpected roles of Hpse2 in bladder physiology, tissue remodeling and Tgfβ signaling. PMID:25510506

  17. Endothelial dysfunction and lung capillary injury in cardiovascular diseases.

    PubMed

    Guazzi, Marco; Phillips, Shane A; Arena, Ross; Lavie, Carl J

    2015-01-01

    Cardiac dysfunction of both systolic and diastolic origins leads to increased left atrial pressure, lung capillary injury and increased resistance to gas transfer. Acutely, pressure-induced trauma disrupts the endothelial and alveolar anatomical configuration and definitively causes an impairment of cellular pathways involved in fluid-flux regulation and gas exchange efficiency, a process well identified as stress failure of the alveolar-capillary membrane. In chronic heart failure (HF), additional stimuli other than pressure may trigger the true remodeling process of capillaries and small arteries characterized by endothelial dysfunction, proliferation of myofibroblasts, fibrosis and extracellular matrix deposition. In parallel there is a loss of alveolar gas diffusion properties due to the increased path from air to blood (thickening of extracellular matrix) and loss of fine molecular mechanism involved in fluid reabsorption and clearance. Deleterious changes in gas transfer not only reflect the underlying lung tissue damage but also portend independent prognostic information and may play a role in the pathogenesis of exercise limitation and ventilatory abnormalities observed in these patients. Few currently approved treatments for chronic HF have the potential to positively affect structural remodeling of the lung capillary network; angiotensin-converting enzyme inhibitors are one of the few currently established options. Recently, more attention has been paid to novel therapies specifically targeting the nitric oxide pathway as a suitable target to improve endothelial function and permeability as well as alveolar gas exchange properties.

  18. [Combination therapy of prostatitis-associated copulative dysfunction].

    PubMed

    Bliumberg, B I; Shatylko, T V; Tverdokhleb, S A; Fomkin, R N; Voskoboĭnikova, I V

    2014-01-01

    Chronic prostatitis is characterized by clinical polymorphism, that may include pain, dysuria, asthenovegetative syndrome, and others. Symptoms associated with impaired copulatory cycle in chronic prostatitis have a significant impact on the quality of life of patient. Sexual dysfunction and sexuality cessation can exacerbate the inflammation of the prostate gland and worsen the underlying disease. The study included 60 patients diagnosed with chronic bacterial prostatitis, complicated by sexual disorders. Patients were divided into two comparable groups of 30 persons. Control group ofpatients received standard antibacterial therapy; study group ofpatients in addition received phytodrug prostanorm. At the end of treatment, higher IIEF-5 scores, increasing number of lecithin granules in the prostate secretion, as well as reducing the severity of irritative symptoms were registered in the study group.

  19. [Cashmere goat bacterial artificial chromosome recombination and cell transfection system].

    PubMed

    Huang, Tian; Cao, Zhongyang; Yang, Yaohui; Cao, Gengsheng

    2016-03-01

    The Cashmere goat is mainly used to produce cashmere, which is very popular for its delicate fiber, luscious softness and natural excellent warm property. Keratin associated protein (KAP) and bone morphogenetic protein (BMP) of the Cashmere goat play an important role in the proliferation and development of cashmere fiber follicle cells. Bacterial artificial chromosome containing kap6.3, kap8.1 and bmp4 genes were used to increase the production and quality of Cashmere. First, we constructed bacterial artificial chromosomes by homology recombination. Then Tol2 transposon was inserted into bacterial artificial chromosomes that were then transfected into Cashmere goat fibroblasts by Amaxa Nucleofector technology according to the manufacture's instructions. We successfully constructed the BAC-Tol2 vectors containing target genes. Each vector contained egfp report gene with UBC promoter, Neomycin resistant gene for cell screening and two loxp elements for resistance removing after transfected into cells. The bacterial artificial chromosome-Tol2 vectors showed a high efficiency of transfection that can reach 1% to 6% with a highest efficiency of 10%. We also obtained Cashmere goat fibroblasts integrated exogenous genes (kap6.3, kap8.1 and bmp4) preparing for the clone of Cashmere goat in the future. Our research demonstrates that the insertion of Tol2 transposons into bacterial artificial chromosomes improves the transfection efficiency and accuracy of bacterial artificial chromosome error-free recombination.

  20. Bacterial Community Structures in Freshwater Polar Environments of Svalbard

    PubMed Central

    Ntougias, Spyridon; Polkowska, Żaneta; Nikolaki, Sofia; Dionyssopoulou, Eva; Stathopoulou, Panagiota; Doudoumis, Vangelis; Ruman, Marek; Kozak, Katarzyna; Namieśnik, Jacek; Tsiamis, George

    2016-01-01

    Two thirds of Svalbard archipelago islands in the High Arctic are permanently covered with glacial ice and snow. Polar bacterial communities in the southern part of Svalbard were characterized using an amplicon sequencing approach. A total of 52,928 pyrosequencing reads were analyzed in order to reveal bacterial community structures in stream and lake surface water samples from the Fuglebekken and Revvatnet basins of southern Svalbard. Depending on the samples examined, bacterial communities at a higher taxonomic level mainly consisted either of Bacteroidetes, Betaproteobacteria, and Microgenomates (OP11) or Planctomycetes, Betaproteobacteria, and Bacteroidetes members, whereas a population of Microgenomates was prominent in 2 samples. At the lower taxonomic level, bacterial communities mostly comprised Microgenomates, Comamonadaceae, Flavobacteriaceae, Legionellales, SM2F11, Parcubacteria (OD1), and TM7 members at different proportions in each sample. The abundance of OTUs shared in common among samples was greater than 70%, with the exception of samples in which the proliferation of Planctomycetaceae, Phycisphaeraceae, and Candidatus Methylacidiphilum spp. lowered their relative abundance. A multi-variable analysis indicated that As, Pb, and Sb were the main environmental factors influencing bacterial profiles. We concluded that the bacterial communities in the polar aquatic ecosystems examined mainly consisted of freshwater and marine microorganisms involved in detritus mineralization, with a high proportion of zooplankton-associated taxa also being identified. PMID:27725345

  1. 15 CFR 12.2 - Undue proliferation.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 15 Commerce and Foreign Trade 1 2010-01-01 2010-01-01 false Undue proliferation. 12.2 Section 12.2 Commerce and Foreign Trade Office of the Secretary of Commerce FAIR PACKAGING AND LABELING § 12.2 Undue proliferation. (a) Information as to possible undue proliferation. Any person or group, including a State or...

  2. Inside the Spiral of Dysfunction: The Personal Consequences of Working for a Dysfunctional Leader

    ERIC Educational Resources Information Center

    Shuck, Brad; Rose, Kevin; Bergman, Matt

    2015-01-01

    Dysfunctional leaders suffocate others with coercive power and ego, are unpredictable, and often lack self-awareness about their dysfunction. Dysfunctional leaders are incredibly difficult to work with and can cause a series of cascading personal consequences for employees who work with them. This Perspectives in Human Resource Development essay…

  3. Inside the Spiral of Dysfunction: The Personal Consequences of Working for a Dysfunctional Leader

    ERIC Educational Resources Information Center

    Shuck, Brad; Rose, Kevin; Bergman, Matt

    2015-01-01

    Dysfunctional leaders suffocate others with coercive power and ego, are unpredictable, and often lack self-awareness about their dysfunction. Dysfunctional leaders are incredibly difficult to work with and can cause a series of cascading personal consequences for employees who work with them. This Perspectives in Human Resource Development essay…

  4. Sleep Dysfunction and Gastrointestinal Diseases.

    PubMed

    Khanijow, Vikesh; Prakash, Pia; Emsellem, Helene A; Borum, Marie L; Doman, David B

    2015-12-01

    Sleep deprivation and impaired sleep quality have been associated with poor health outcomes. Many patients experience sleep disturbances, which can increase the risk of medical conditions such as hypertension, obesity, stroke, and heart disease as well as increase overall mortality. Recent studies have suggested that there is a strong association between sleep disturbances and gastrointestinal diseases. Proinflammatory cytokines, such as tumor necrosis factor, interleukin-1, and interleukin-6, have been associated with sleep dysfunction. Alterations in these cytokines have been seen in certain gastrointestinal diseases, such as gastroesophageal reflux disease, inflammatory bowel disease, liver disorders, and colorectal cancer. It is important for gastroenterologists to be aware of the relationship between sleep disorders and gastrointestinal illnesses to ensure good care for patients. This article reviews the current research on the interplay between sleep disorders, immune function, and gastrointestinal diseases.

  5. Ulnar intrinsic anatomy and dysfunction.

    PubMed

    Dell, Paul C; Sforzo, Christopher R

    2005-01-01

    Normal hand function is a balance between the extrinsic and intrinsic musculature. Although individually the intrinsics are small muscles in diameter, collectively they represent a large muscle that contributes approximately 50% of grip strength. Dysfunction of the intrinsics consequently leads to impaired grip and pinch strength as well recognized deformities. Low ulnar nerve palsy preserves ulnar innervated extrinsics resulting in sensory loss, digital clawing, thumb deformity, abduction of the small finger, and asynchronous finger motion. High ulnar nerve palsy is characterized by the above plus paralysis of the ulnar profundi and the flexor carpi ulnaris. Understanding the normal anatomy allows the clinician to identify the site of the lesion and plan appropriate surgical intervention. This article revisits the classic work of Richard J. Smith on ulnar nerve palsy with contemporary perspective.

  6. Hypoparathyroidism presenting as cognitive dysfunction

    PubMed Central

    Kumar, Gunjan; Kaur, Darshpreet; Aggarwal, Puneet; Khurana, Tilak

    2013-01-01

    Metabolic dysfunction in hypoparathyroidism is an important cause of intracranial calcifications, which cause cognitive impairment depending on the calcified areas leading to difficulties in executing activities of daily living. We report a case of a 25-year-old man who presented with gradually decreasing organisational skills, memory problems and difficulty in carrying out daily activities. CT imaging of the brain showed extensive calcification in the basal ganglia and cerebral white matter. Comprehensive health-related quality of life and cognitive assessment revealed significant affliction in his activities of daily living along with impairment in recall memory, executive functions and verbal fluency. Owing to late diagnosis, chronicity of cognitive problems could not prevent him from discontinuing his college education. PMID:23709145

  7. Postoperative delirium and cognitive dysfunction.

    PubMed

    Deiner, S; Silverstein, J H

    2009-12-01

    Postoperative delirium and cognitive dysfunction (POCD) are topics of special importance in the geriatric surgical population. They are separate entities, whose relationship has yet to be fully elucidated. Although not limited to geriatric patients, the incidence and impact of both are more profound in geriatric patients. Delirium has been shown to be associated with longer and more costly hospital course and higher likelihood of death within 6 months or postoperative institutionalization. POCD has been associated with increased mortality, risk of leaving the labour market prematurely, and dependency on social transfer payments. Here, we review their definitions and aetiology, and discuss treatment and prevention in elderly patients undergoing major non-cardiac surgery. Good basic care demands identification of at-risk patients, awareness of common perioperative aggravating factors, simple prevention interventions, recognition of the disease states, and basic treatments for patients with severe hyperactive manifestations.

  8. Pharmacotherapeutic management of erectile dysfunction.

    PubMed

    Hawksworth, D J; Burnett, A L

    2015-12-01

    Erectile dysfunction is a common condition in aging men and significantly affects their quality of life and interpersonal relationships. Its prevalence and incidence are associated with aging, lifestyle factors and cardiovascular comorbidities. Preoccupation with male virility has been present for centuries, and a wide variety of herbs and potions have been used to treat any sexual deficiencies. Recent major advances in understanding of erectile physiology and pathophysiology led to development of currently available systemic and local pharmacotherapies. They are designed to work either centrally or peripherally and to either suppress anti-erectile mechanisms, enhance the pro-erectile ones or influence both. Since all the current formulations have variable safety and efficacy profiles, the search for highly specific, simple, convenient and clinically effective impotence treatments or prophylactics continues.

  9. Flibanserin for female sexual dysfunction.

    PubMed

    Reviriego, C

    2014-08-01

    Hypoactive sexual desire disorder (HSDD) is the most commonly described form of female sexual dysfunction. There is currently no pharmacological therapy approved to treat HSDD, and therefore, there is an unmet medical need for the development of efficacious treatment alternatives. Flibanserin is a novel, non-hormonal drug for the treatment of HSDD in pre- and postmenopausal women, although the application submitted to the U.S. Food and Drug Administration by Sprout Pharmaceuticals is only for premenopausal women. Flibanserin works by correcting an imbalance of the levels of the neurotransmitters that affect sexual desire. More specifically, flibanserin increases dopamine and norepinephrine, both responsible for sexual excitement, and decreases serotonin, responsible for sexual inhibition. Clinically, flibanserin has exhibited some encouraging results in terms of its ability to increase the frequency of satisfying sexual events, and the intensity of sexual desire. However, adverse events such as dizziness, nausea, fatigue and somnolence, typical of a centrally acting drug, are also frequently related to flibanserin treatment.

  10. Coronary microvascular dysfunction: an update

    PubMed Central

    Crea, Filippo; Camici, Paolo G.; Bairey Merz, Cathleen Noel

    2014-01-01

    Many patients undergoing coronary angiography because of chest pain syndromes, believed to be indicative of obstructive atherosclerosis of the epicardial coronary arteries, are found to have normal angiograms. In the past two decades, a number of studies have reported that abnormalities in the function and structure of the coronary microcirculation may occur in patients without obstructive atherosclerosis, but with risk factors or with myocardial diseases as well as in patients with obstructive atherosclerosis; furthermore, coronary microvascular dysfunction (CMD) can be iatrogenic. In some instances, CMD represents an epiphenomenon, whereas in others it is an important marker of risk or may even contribute to the pathogenesis of cardiovascular and myocardial diseases, thus becoming a therapeutic target. This review article provides an update on the clinical relevance of CMD in different clinical settings and also the implications for therapy. PMID:24366916

  11. Hypoparathyroidism presenting as cognitive dysfunction.

    PubMed

    Kumar, Gunjan; Kaur, Darshpreet; Aggarwal, Puneet; Khurana, Tilak

    2013-05-23

    Metabolic dysfunction in hypoparathyroidism is an important cause of intracranial calcifications, which cause cognitive impairment depending on the calcified areas leading to difficulties in executing activities of daily living. We report a case of a 25-year-old man who presented with gradually decreasing organisational skills, memory problems and difficulty in carrying out daily activities. CT imaging of the brain showed extensive calcification in the basal ganglia and cerebral white matter. Comprehensive health-related quality of life and cognitive assessment revealed significant affliction in his activities of daily living along with impairment in recall memory, executive functions and verbal fluency. Owing to late diagnosis, chronicity of cognitive problems could not prevent him from discontinuing his college education.

  12. Psychopathy: cognitive and neural dysfunction.

    PubMed

    R Blair, R James

    2013-06-01

    Psychopathy is a developmental disorder marked by emotional deficits and an increased risk for antisocial behavior. It is not equivalent to the diagnosis Antisocial Personality Disorder, which concentrates only on the increased risk for antisocial behavior and not a specific cause-ie, the reduced empathy and guilt that constitutes the emotional deficit. The current review considers data from adults with psychopathy with respect to the main cognitive accounts of the disorder that stress either a primary attention deficit or a primary emotion deficit. In addition, the current review considers data regarding the neurobiology of this disorder. Dysfunction within the amygdala's role in reinforcement learning and the role of ventromedial frontal cortex in the representation of reinforcement value is stressed. Data is also presented indicating potential difficulties within parts of temporal and posterior cingulate cortex. Suggestions are made with respect to why these deficits lead to the development of the disorder.

  13. Sleep Dysfunction and Gastrointestinal Diseases

    PubMed Central

    Khanijow, Vikesh; Prakash, Pia; Emsellem, Helene A.; Borum, Marie L.

    2015-01-01

    Sleep deprivation and impaired sleep quality have been associated with poor health outcomes. Many patients experience sleep disturbances, which can increase the risk of medical conditions such as hypertension, obesity, stroke, and heart disease as well as increase overall mortality. Recent studies have suggested that there is a strong association between sleep disturbances and gastrointestinal diseases. Proinflammatory cytokines, such as tumor necrosis factor, interleukin-1, and interleukin-6, have been associated with sleep dysfunction. Alterations in these cytokines have been seen in certain gastrointestinal diseases, such as gastroesophageal reflux disease, inflammatory bowel disease, liver disorders, and colorectal cancer. It is important for gastroenterologists to be aware of the relationship between sleep disorders and gastrointestinal illnesses to ensure good care for patients. This article reviews the current research on the interplay between sleep disorders, immune function, and gastrointestinal diseases. PMID:27134599

  14. Pharmacologic Treatment of Erectile Dysfunction

    PubMed Central

    Steers, William D

    2002-01-01

    Penile erection occurs in response to cavernous smooth muscle relaxation, increased blood flow to the penis, and restriction of venous outflow. These events are regulated by a spinal reflex relying on visual, imaginative, and olfactory stimuli generated within the central nervous system (CNS) and on tactile stimuli to the penis. Drugs can have a facilitatory or inhibitory effect either on the nerves regulating this reflex or on the cavernous smooth muscle. A balance between contractile and relaxant factors governs flaccidity/rigidity within the penis. Drugs that raise cytosolic calcium either prevent or abort erection. Conversely, drugs that lower cytosolic calcium relax smooth muscle and can initiate penile erection. Efficacy in treating erectile dysfunction (ED) with phosphodiesterase inhibitors, especially type 5; α-adrenergic-receptor antagonists; and dopamine agonists exploit these mechanisms within the penis or CNS. Recent advances in our understanding of the pharmacology of penile erection are being translated into effective therapies for ED. PMID:16986010

  15. Psychopathy: cognitive and neural dysfunction

    PubMed Central

    R. Blair, R. James

    2013-01-01

    Psychopathy is a developmental disorder marked by emotional deficits and an increased risk for antisocial behavior. It is not equivalent to the diagnosis Antisocial Personality Disorder, which concentrates only on the increased risk for antisocial behavior and not a specific cause—ie, the reduced empathy and guilt that constitutes the emotional deficit. The current review considers data from adults with psychopathy with respect to the main cognitive accounts of the disorder that stress either a primary attention deficit or a primary emotion deficit. In addition, the current review considers data regarding the neurobiology of this disorder. Dysfunction within the amygdala's role in reinforcement learning and the role of ventromedial frontal cortex in the representation of reinforcement value is stressed. Data is also presented indicating potential difficulties within parts of temporal and posterior cingulate cortex. Suggestions are made with respect to why these deficits lead to the development of the disorder. PMID:24174892

  16. Oral sensory dysfunction following radiotherapy.

    PubMed

    Bearelly, Shethal; Wang, Steven J; Cheung, Steven W

    2017-10-01

    To assess differences in oral tactile sensation between subjects who have undergone radiation therapy (XRT) compared to healthy controls. Cross-sectional cohort comparison. Thirty-four subjects with a history of XRT were compared with 23 healthy controls. There was no difference in age (P = .23), but there were slightly more males in the XRT cohort (P = .03). The mean (standard deviation) time after XRT completion was 3.84 (4.84) years. Fifty-six percent of the XRT cohort received chemotherapy. Using our previously validated methodology to measure oral tactile sensory threshold quantitatively with Cheung-Bearelly monofilaments, sensory thresholds of four subsites (anterior tongue, buccal mucosa, posterior tongue, soft palate) were compared for the two cohorts. Site-by-site comparisons showed higher forces were required for stimulus detection at all four subsites among subjects in the XRT cohort compared to healthy controls. Mean force in grams for XRT versus control cohorts were: anterior tongue, 0.39 (1.0) versus 0.02 (0.01); buccal mucosa, 0.42 (0.95) versus 0.06 (0.05); posterior tongue, 0.76 (1.46) versus 0.10 (0.07); and soft palate, 0.86 (1.47) versus 0.08 (0.05) (P < .001 for all comparisons). Combining all four subsites into a single metric to assess an overall level of oral tactile dysfunction, the XRT cohort had reduced sensation by 18.7 dB (P < .001). After radiation therapy, the oral cavity and oropharynx exhibit global tactile sensory dysfunction, manifested by increased tactile forces required for stimulus detection. The magnitude of sensory impairment is 18.7 dB. 3b. Laryngoscope, 127:2282-2286, 2017. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

  17. Bacterial extracellular lignin peroxidase

    DOEpatents

    Crawford, Donald L.; Ramachandra, Muralidhara

    1993-01-01

    A newly discovered lignin peroxidase enzyme is provided. The enzyme is obtained from a bacterial source and is capable of degrading the lignin portion of lignocellulose in the presence of hydrogen peroxide. The enzyme is extracellular, oxidative, inducible by lignin, larch wood xylan, or related substrates and capable of attacking certain lignin substructure chemical bonds that are not degradable by fungal lignin peroxidases.

  18. BACTERIAL WATERBORNE PATHOGENS

    EPA Science Inventory

    Bacterial pathogens are examples of classical etiological agents of waterborne disease. While these agents no longer serve as major threats to U.S. water supplies, they are still important pathogens in areas with substandard sanitation and poor water treatment facilities. In th...

  19. Proteases in bacterial pathogenesis.

    PubMed

    Ingmer, Hanne; Brøndsted, Lone

    2009-11-01

    Bacterial pathogens rely on proteolysis for protein quality control under adverse conditions experienced in the host, as well as for the timely degradation of central virulence regulators. We have focused on the contribution of the conserved Lon, Clp, HtrA and FtsH proteases to pathogenesis and have highlighted common biological processes for which their activities are important for virulence.

  20. Bacterial inclusion body purification.

    PubMed

    Seras-Franzoso, Joaquin; Peternel, Spela; Cano-Garrido, Olivia; Villaverde, Antonio; García-Fruitós, Elena

    2015-01-01

    Purification of bacterial inclusion bodies (IBs) is gaining importance due to the raising of novel applications for this type of submicron particulate protein clusters, with potential uses in the biomedical field among others. Here, we present two optimized methods to purify IBs adapting classical procedures to the material nature as well as the requirements of its final application.

  1. Bacterial leaf spot

    USDA-ARS?s Scientific Manuscript database

    Bacterial leaf spot has been reported in Australia (Queensland), Egypt, El Salvador, India, Japan, Nicaragua, Sudan, and the United States (Florida, Iowa, Kansas, Maryland, and Wisconsin). It occasionally causes locally severe defoliation and post-emergence damping-off and stunting. The disease is...

  2. BACTERIAL WATERBORNE PATHOGENS

    EPA Science Inventory

    Bacterial pathogens are examples of classical etiological agents of waterborne disease. While these agents no longer serve as major threats to U.S. water supplies, they are still important pathogens in areas with substandard sanitation and poor water treatment facilities. In th...

  3. Bacterial microflora of nectarines

    USDA-ARS?s Scientific Manuscript database

    Microflora of fruit surfaces has been the best source of antagonists against fungi causing postharvest decays of fruit. However, there is little information on microflora colonizing surfaces of fruits other than grapes, apples, and citrus fruit. We characterized bacterial microflora on nectarine f...

  4. [Spontaneous bacterial peritonitis].

    PubMed

    Velkey, Bálint; Vitális, Eszter; Vitális, Zsuzsanna

    2017-01-01

    Spontaneous bacterial peritonitis occurs most commonly in cirrhotic patients with ascites. Pathogens get into the circulation by intestinal translocation and colonize in peritoneal fluid. Diagnosis of spontaneous bacterial peritonitis is based on elevated polymorphonuclear leukocyte count in the ascites (>0,25 G/L). Ascites culture is often negative but aids to get information about antibiotic sensitivity in positive cases. Treatment in stable patient can be intravenous then orally administrated ciprofloxacin or amoxicillin/clavulanic acid, while in severe cases intravenous III. generation cephalosporin. Nosocomial spontaneous bacterial peritonitis often caused by Gram-positive bacteria and multi-resistant pathogens can also be expected thus carbapenem should be the choice of the empiric treatment. Antibiotic prophylaxis should be considered. Norfloxacin is used most commonly, but changes are expected due to increase in quinolone resistance. As a primary prophylaxis, a short-term antibiotic treatment is recommended after gastrointestinal bleeding for 5 days, while long-term prophylaxis is for patients with low ascites protein, and advanced disease (400 mg/day). Secondary prophylaxis is recommended for all patients recovered from spontaneous bacterial peritonitis. Due to increasing antibiotic use of antibiotics prophylaxis is debated to some degree. Orv. Hetil., 2017, 158(2), 50-57.

  5. Modeling intraocular bacterial infections.

    PubMed

    Astley, Roger A; Coburn, Phillip S; Parkunan, Salai Madhumathi; Callegan, Michelle C

    2016-09-01

    Bacterial endophthalmitis is an infection and inflammation of the posterior segment of the eye which can result in significant loss of visual acuity. Even with prompt antibiotic, anti-inflammatory and surgical intervention, vision and even the eye itself may be lost. For the past century, experimental animal models have been used to examine various aspects of the pathogenesis and pathophysiology of bacterial endophthalmitis, to further the development of anti-inflammatory treatment strategies, and to evaluate the pharmacokinetics and efficacies of antibiotics. Experimental models allow independent control of many parameters of infection and facilitate systematic examination of infection outcomes. While no single animal model perfectly reproduces the human pathology of bacterial endophthalmitis, investigators have successfully used these models to understand the infectious process and the host response, and have provided new information regarding therapeutic options for the treatment of bacterial endophthalmitis. This review highlights experimental animal models of endophthalmitis and correlates this information with the clinical setting. The goal is to identify knowledge gaps that may be addressed in future experimental and clinical studies focused on improvements in the therapeutic preservation of vision during and after this disease. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. The Bacterial Growth Curve.

    ERIC Educational Resources Information Center

    Paulton, Richard J. L.

    1991-01-01

    A procedure that allows students to view an entire bacterial growth curve during a two- to three-hour student laboratory period is described. Observations of the lag phase, logarithmic phase, maximum stationary phase, and phase of decline are possible. A nonpathogenic, marine bacterium is used in the investigation. (KR)

  7. Antibiotics May Trigger Mitochondrial Dysfunction Inducing Psychiatric Disorders

    PubMed Central

    Stefano, George B.; Samuel, Joshua; Kream, Richard M.

    2017-01-01

    Clinical usage of several classes of antibiotics is associated with moderate to severe side effects due to the promotion of mitochondrial dysfunction. We contend that this may be due to perturbation of unique evolutionary relationships that link selective biochemical and molecular aspects of mitochondrial biology to conserved enzymatic processes derived from bacterial progenitors. Operationally, stereo-selective conformational matching between mitochondrial respiratory complexes, cytosolic and nuclear signaling complexes appears to support the conservation of a critically important set of chemical messengers required for existential regulation of homeostatic cellular processes. Accordingly, perturbation of normative mitochondrial function by select classes of antibiotics is certainly reflective of the high degree of evolutionary pressure designed to maintain ongoing bidirectional signaling processes between cellular compartments. These issues are of critical importance in evaluating potentially severe side effects of antibiotics on complex behavioral functions mediated by CNS neuronal groups. The CNS is extremely dependent on delivery of molecular oxygen for maintaining a required level of metabolic activity, as reflected by the high concentration of neuronal mitochondria. Thus, it is not surprising to find several distinct behavioral abnormalities conforming to established psychiatric criteria that are associated with antibiotic usage in humans. The manifestation of acute and/or chronic psychiatric conditions following antibiotic usage may provide unique insights into key etiological factors of major psychiatric syndromes that involve rundown of cellular bioenergetics via mitochondrial dysfunction. Thus, a potential window of opportunity exists for development of novel therapeutic agents targeting diminished mitochondrial function as a factor in severe behavioral disorders. PMID:28063266

  8. On the Etiology of Sexual Dysfunction

    ERIC Educational Resources Information Center

    Apfelbaum, Bernard

    1977-01-01

    Lack of consideration of the sexually functional population has led to misconceptions about causes of sexual dysfunction functioning. Automatic functioning can mask effects of pathogenic influences on sexuality, making these effects appear random, confounding etiological issues and creating the belief that causes of sexual dysfunction and disorder…

  9. On the Etiology of Sexual Dysfunction

    ERIC Educational Resources Information Center

    Apfelbaum, Bernard

    1977-01-01

    Lack of consideration of the sexually functional population has led to misconceptions about causes of sexual dysfunction functioning. Automatic functioning can mask effects of pathogenic influences on sexuality, making these effects appear random, confounding etiological issues and creating the belief that causes of sexual dysfunction and disorder…

  10. Male Pseudoheterosexuality and Minimal Sexual Dysfunction

    ERIC Educational Resources Information Center

    Gutstadt, Joseph P.

    1976-01-01

    There is often a correlation between "pseudoheterosexuality" and minor sexual dysfunction. Insight alone is not sufficient to provide relief, but when the patient can be helped to a comfortable acceptance of his homosexual feelings as a normal and healthy facet of his personality, very often the dysfunction is relieved. (Author)

  11. Psychosocial Dysfunction in Adults with Epilepsy.

    ERIC Educational Resources Information Center

    Pershad, Dwarka; Siddiqui, Razia S.

    1992-01-01

    This study examined the amount of psychosocial disturbance experienced by adults (n=53) in India with epilepsy, as well as the relationship between psychosocial dysfunction, duration of illness, and computerized axial tomography findings. Results indicated that three-quarters exhibited no or very mild psychosocial dysfunction. (DB)

  12. Clinical signs in diffuse cerebral dysfunction.

    PubMed Central

    Jenkyn, L R; Walsh, D B; Culver, C M; Reeves, A G

    1977-01-01

    Abnormal responses to 13 questions from a typical mental status examination and 32 signs of neurological dysfunction were correlated with increasing degrees of cognitive impairment as measured by the Halstead-Reitan Neuropsychological Battery. Thirteen of these factors were found to be useful predictors of diffuse cerebral dysfunction when combined into a brief screening examination for application at the bedside. PMID:591973

  13. Cellular Dysfunction in the Diabetic Fibroblast

    PubMed Central

    Lerman, Oren Z.; Galiano, Robert D.; Armour, Mary; Levine, Jamie P.; Gurtner, Geoffrey C.

    2003-01-01

    Although it is known that systemic diseases such as diabetes result in impaired wound healing, the mechanism for this impairment is not understood. Because fibroblasts are essential for wound repair, we compared the in vitro behavior of fibroblasts cultured from diabetic, leptin receptor-deficient (db/db) mice with wild-type fibroblasts from mice of the same genetic background in processes important during tissue repair. Adult diabetic mouse fibroblast migration exhibited a 75% reduction in migration compared to normal fibroblasts (P < 0.001) and was not significantly stimulated by hypoxia (1% O2), whereas wild-type fibroblast migration was up-regulated nearly twofold in hypoxic conditions (P < 0.05). Diabetic fibroblasts produced twice the amount of pro-matrix metalloproteinase-9 as normal fibroblasts, as measured by both gelatin zymography and enzyme-linked immunosorbent assay (P < 0.05). Adult diabetic fibroblasts exhibited a sevenfold impairment in vascular endothelial growth factor (VEGF) production (4.5 ± 1.3 pg/ml versus 34.8 ± 3.3 pg/ml, P < 0.001) compared to wild-type fibroblasts. Moreover, wild-type fibroblast production of VEGF increased threefold in response to hypoxia, whereas diabetic fibroblast production of VEGF was not up-regulated in hypoxic conditions (P < 0.001). To address the question whether these differences resulted from chronic hyperglycemia or absence of the leptin receptor, fibroblasts were harvested from newborn db/db mice before the onset of diabetes (4 to 5 weeks old). These fibroblasts showed no impairments in VEGF production under basal or hypoxic conditions, confirming that the results from db/db fibroblasts in mature mice resulted from the diabetic state and were not because of alterations in the leptin-leptin receptor axis. Markers of cellular viability including proliferation and senescence were not significantly different between diabetic and wild-type fibroblasts. We conclude that, in vitro, diabetic fibroblasts show

  14. Counter-proliferation and Non-proliferation: Both Needed

    NASA Astrophysics Data System (ADS)

    May, Michael

    2004-03-01

    Preventing further proliferation of nuclear weapon and nuclear weapons usable materials, and securing the weapons and materials that exist, have increased in importance with the increased urgency of the fight against international terrorism. This problem is likely to continue to increase in importance with the anticipated growth of nuclear civilian applications around the world. Recent experience in North Korea, Iraq and Iran tends to show that some combination of counterproliferation and better use of traditional, multilateral non-proliferation methods provides the best way to address this problem. Governments seeking nuclear civilian applications, particularly those that are suspicious of Western motives, must be offered in parallel an attractive way into the system should they follow its rules and an unacceptable alternative should they not. Such a combination should aim at implementing specific measures to (1) secure nuclear materials, (2) monitor dual-use facilities, (3) improve international governance of treaties and other agreements, and (4) reduce the demand for nuclear weapons. For some of the measures implementation has begun, although with less money and priority than is needed. Other measures would constitute a major departure from the way civilian nuclear activities are now carried out and remain controversial. The established nuclear powers must agree on implementation and funding of the measures suggested before there can be much progress elsewhere.

  15. Mechanisms Used for Genomic Proliferation by Thermophilic Group II Introns

    PubMed Central

    Mohr, Georg; Ghanem, Eman; Lambowitz, Alan M.

    2010-01-01

    Mobile group II introns, which are found in bacterial and organellar genomes, are site-specific retroelments hypothesized to be evolutionary ancestors of spliceosomal introns and retrotransposons in higher organisms. Most bacteria, however, contain no more than one or a few group II introns, making it unclear how introns could have proliferated to higher copy numbers in eukaryotic genomes. An exception is the thermophilic cyanobacterium Thermosynechococcus elongatus, which contains 28 closely related copies of a group II intron, constituting ∼1.3% of the genome. Here, by using a combination of bioinformatics and mobility assays at different temperatures, we identified mechanisms that contribute to the proliferation of T. elongatus group II introns. These mechanisms include divergence of DNA target specificity to avoid target site saturation; adaptation of some intron-encoded reverse transcriptases to splice and mobilize multiple degenerate introns that do not encode reverse transcriptases, leading to a common splicing apparatus; and preferential insertion within other mobile introns or insertion elements, which provide new unoccupied sites in expanding non-essential DNA regions. Additionally, unlike mesophilic group II introns, the thermophilic T. elongatus introns rely on elevated temperatures to help promote DNA strand separation, enabling access to a larger number of DNA target sites by base pairing of the intron RNA, with minimal constraint from the reverse transcriptase. Our results provide insight into group II intron proliferation mechanisms and show that higher temperatures, which are thought to have prevailed on Earth during the emergence of eukaryotes, favor intron proliferation by increasing the accessibility of DNA target sites. We also identify actively mobile thermophilic introns, which may be useful for structural studies, gene targeting in thermophiles, and as a source of thermostable reverse transcriptases. PMID:20543989

  16. Pmp27 promotes peroxisomal proliferation

    PubMed Central

    1995-01-01

    Peroxisomes perform many essential functions in eukaryotic cells. The weight of evidence indicates that these organelles divide by budding from preexisting peroxisomes. This process is not understood at the molecular level. Peroxisomal proliferation can be induced in Saccharomyces cerevisiae by oleate. This growth substrate is metabolized by peroxisomal enzymes. We have identified a protein, Pmp27, that promotes peroxisomal proliferation. This protein, previously termed Pmp24, was purified from peroxisomal membranes, and the corresponding gene, PMP27, was isolated and sequenced. Pmp27 shares sequence similarity with the Pmp30 family in Candida boidinii. Pmp27 is a hydrophobic peroxisomal membrane protein but it can be extracted by high pH, suggesting that it does not fully span the bilayer. Its expression is regulated by oleate. The function of Pmp27 was probed by observing the phenotype of strains in which the protein was eliminated by gene disruption or overproduced by expression from a multicopy plasmid. The strain containing the disruption (3B) was able to grow on all carbon sources tested, including oleate, although growth on oleate, glycerol, and acetate was slower than wild type. Strain 3B contained peroxisomes with all of the enzymes of beta-oxidation. However, in addition to the presence of a few modestly sized peroxisomes seen in a typical thin section of a cell growing on oleate-containing medium, cells of strain 3B also contained one or two very large peroxisomes. In contrast, cells in a strain in which Pmp27 was overexpressed contained an increased number of normal-sized peroxisomes. We suggest that Pmp27 promotes peroxisomal proliferation by participating in peroxisomal elongation or fission. PMID:7721939

  17. Pathophysiology of bladder dysfunction in Parkinson's disease.

    PubMed

    Sakakibara, Ryuji; Tateno, Fuyuki; Kishi, Masahiko; Tsuyuzaki, Yohei; Uchiyama, Tomoyuki; Yamamoto, Tatsuya

    2012-06-01

    Bladder dysfunction (urinary urgency/frequency) is a common non-motor disorder in Parkinson's disease (PD). In contrast to motor disorders, bladder dysfunction is sometimes non-responsive to levodopa treatment. The brain pathology causing the bladder dysfunction (appearance of overactivity) involves an altered dopamine basal ganglia-frontal circuit, which normally suppresses the micturition reflex. The pathophysiology of the bladder dysfunction in PD differs from that in multiple system atrophy; therefore, it might aid in differential diagnosis. Anticholinergic agents are used to treat bladder dysfunction in PD, although these drugs should be used with caution particularly in elderly patients who have cognitive decline. These treatments might be beneficial in maximizing the patients' quality of life.

  18. Endothelial Dysfunction in Renal Failure: Current Update.

    PubMed

    Radenkovic, Miroslav; Stojanovic, Marko; Prostran, Milica

    2016-01-01

    Endothelial dysfunction is principally characterized by impaired endothelium- dependent transduction mechanisms related to vascular relaxation, as an outcome of decreased release of endothelium-derived relaxing factors, mainly nitric oxide, as well as augmented oxidative stress, increased inflammation and predominance of vascular action produced by endothelium-derived contracting factors. Current data strongly suggest that pathological development of different types of kidney impairment with further progression to renal failure includes notable vascular changes associated with endothelial dysfunction. In accordance, this scientific field represents an advancing area of investigation, involving different biomarkers of endothelial dysfunction linked to renal impairment, as well as clinical findings with new information that can provide a more comprehensive understanding of the role of endothelial dysfunction in kidney disease. With regards to quoted facts, the aim of this article was to review the latest data related to endothelial dysfunction and renal failure by selection of relevant articles released from 2010 to 2015.

  19. Attachment, borderline personality, and romantic relationship dysfunction.

    PubMed

    Hill, Jonathan; Stepp, Stephanie D; Wan, Ming Wai; Hope, Holly; Morse, Jennifer Q; Steele, Miriam; Steele, Howard; Pilkonis, Paul A

    2011-12-01

    Previous studies have implicated attachment and disturbances in romantic relationships as important indicators for Borderline Personality Disorder (BPD). The current research extends our current knowledge by examining the specific associations among attachment, romantic relationship dysfunction, and BPD, above and beyond the contribution of emotional distress and nonromantic interpersonal functioning in two distinct samples. Study 1 comprised a community sample of women (N = 58) aged 25-36. Study 2 consisted of a psychiatric sample (N = 138) aged 21-60. Results from both Study 1 and Study 2 demonstrated that (1) attachment was specifically related to BPD symptoms and romantic dysfunction, (2) BPD symptoms were specifically associated with romantic dysfunction, and (3) the association between attachment and romantic dysfunction was statistically mediated by BPD symptoms. The findings support specific associations among attachment, BPD symptoms, and romantic dysfunction.

  20. ATTACHMENT, BORDERLINE PERSONALITY, AND ROMANTIC RELATIONSHIP DYSFUNCTION

    PubMed Central

    Hill, Jonathan; Stepp, Stephanie D.; Wan, Ming Wai; Hope, Holly; Morse, Jennifer Q.; Steele, Miriam; Steele, Howard; Pilkonis, Paul A.

    2014-01-01

    Previous studies have implicated attachment and disturbances in romantic relationships as important indicators for Borderline Personality Disorder (BPD). The current research extends our current knowledge by examining the specific associations among attachment, romantic relationship dysfunction, and BPD, above and beyond the contribution of emotional distress and nonromantic interpersonal functioning in two distinct samples. Study 1 comprised a community sample of women (N = 58) aged 25–36. Study 2 consisted of a psychiatric sample (N = 138) aged 21–60. Results from both Study 1 and Study 2 demonstrated that (1) attachment was specifically related to BPD symptoms and romantic dysfunction, (2) BPD symptoms were specifically associated with romantic dysfunction, and (3) the association between attachment and romantic dysfunction was statistically mediated by BPD symptoms. The findings support specific associations among attachment, BPD symptoms, and romantic dysfunction. PMID:22217225

  1. Understanding taste dysfunction in patients with cancer.

    PubMed

    McLaughlin, Laura; Mahon, Suzanne M

    2012-04-01

    Taste dysfunction is a significant but underestimated issue for patients with cancer. Impaired taste results in changes in diet and appetite, early satiety, and impaired social interactions. Nurses can play a key role in educating patients and families on the pathophysiology of taste dysfunction by suggesting interventions to treat the consequences of taste dysfunction, when available, and offering psychosocial support as patients cope with this often devastating consequence of treatment. Taste recognition helps humans identify the nutritional quality of food and signals the digestive tract to begin secreting enzymes. Spoiled or tainted foods typically are recognized by their bad taste. Along with the other sensory systems, taste is crucial for helping patients treated for cancer feel normal. This article will review the anatomy and physiology of taste; define the different types of taste dysfunction, including the underlying pathophysiologic basis related to cancer treatment; and discuss potential nursing interventions to manage the consequences of taste dysfunction.

  2. Diastolic dysfunction in the critically ill patient.

    PubMed

    Suárez, J C; López, P; Mancebo, J; Zapata, L

    2016-11-01

    Left ventricular diastolic dysfunction is a common finding in critically ill patients. It is characterized by a progressive deterioration of the relaxation and the compliance of the left ventricle. Two-dimensional and Doppler echocardiography is a cornerstone in its diagnosis. Acute pulmonary edema associated with hypertensive crisis is the most frequent presentation of diastolic dysfunction critically ill patients. Myocardial ischemia, sepsis and weaning failure from mechanical ventilation also may be associated with diastolic dysfunction. The treatment is based on the reduction of pulmonary congestion and left ventricular filling pressures. Some studies have found a prognostic role of diastolic dysfunction in some diseases such as sepsis. The present review aims to analyze thoroughly the echocardiographic diagnosis and the most frequent scenarios in critically ill patients in whom diastolic dysfunction plays a key role. Copyright © 2016 Elsevier España, S.L.U. y SEMICYUC. All rights reserved.

  3. Proliferation Resistance and the Nuclear Renaissance

    SciTech Connect

    Shea, Thomas E.; Zentner, Michael D.

    2008-05-01

    This article explores how emphasizing proliferation resistance will accomplish that goal. What does it mean for a nuclear fuel cycle to be resistant to proliferation? How can the risk of proliferation from a fuel cycle be evaluated? How has proliferation been considered in the past and how is it being considered in nuclear energy development programs today? How should proliferation concerns interact with facility safety and operations? How do proliferation concerns affect the prospects for nuclear energy in the 21st century? And finally, what is the thinking today in relation to deployment arrangements, technical measures, and R&D programs that are in place or proposed that could both decrease the risk of proliferation and ensure the successful renaissance of nuclear power.

  4. Atrial natriuretic peptide protects against Staphylococcus aureus-induced lung injury and endothelial barrier dysfunction

    PubMed Central

    Xing, Junjie; Moldobaeva, Nurgul

    2011-01-01

    Lung inflammation and alterations in endothelial cell (EC) permeability are key events to development of acute lung injury (ALI). Protective effects of atrial natriuretic peptide (ANP) have been shown against inflammatory signaling and endothelial barrier dysfunction induced by gram-negative bacterial wall liposaccharide. We hypothesized that ANP may possess more general protective effects and attenuate lung inflammation and EC barrier dysfunction by suppressing inflammatory cascades and barrier-disruptive mechanisms shared by gram-negative and gram-positive pathogens. C57BL/6J wild-type or ANP knockout mice (Nppa−/−) were treated with gram-positive bacterial cell wall compounds, Staphylococcus aureus-derived peptidoglycan (PepG) and/or lipoteichoic acid (LTA) (intratracheal, 2.5 mg/kg each), with or without ANP (intravenous, 2 μg/kg). In vitro, human pulmonary EC barrier properties were assessed by morphological analysis of gap formation and measurements of transendothelial electrical resistance. LTA and PepG markedly increased pulmonary EC permeability and activated p38 and ERK1/2 MAP kinases, NF-κB, and Rho/Rho kinase signaling. EC barrier dysfunction was further elevated upon combined LTA and PepG treatment, but abolished by ANP pretreatment. In vivo, LTA and PepG-induced accumulation of protein and cells in the bronchoalveolar lavage fluid, tissue neutrophil infiltration, and increased Evans blue extravasation in the lungs was significantly attenuated by intravenous injection of ANP. Accumulation of bronchoalveolar lavage markers of LTA/PepG-induced lung inflammation and barrier dysfunction was further augmented in ANP−/− mice and attenuated by exogenous ANP injection. These results strongly suggest a protective role of ANP in the in vitro and in vivo models of ALI associated with gram-positive infection. Thus ANP may have important implications in therapeutic strategies aimed at the treatment of sepsis and ALI-induced gram-positive bacterial

  5. Role of mitochondrial dysfunction in hyperglycaemia-induced coronary microvascular dysfunction: Protective role of resveratrol.

    PubMed

    Joshi, Mandar S; Williams, David; Horlock, Duncan; Samarasinghe, Thilini; Andrews, Karen L; Jefferis, Ann-Maree; Berger, Philip J; Chin-Dusting, Jaye P; Kaye, David M

    2015-05-01

    Microvascular complications are now recognized to play a major role in diabetic complications, and understanding the mechanisms is critical. Endothelial dysfunction occurs early in the course of the development of complications; the precise mechanisms remain poorly understood. Mitochondrial dysfunction may occur in a diabetic rat heart and may act as a source of the oxidative stress. However, the role of endothelial cell-specific mitochondrial dysfunction in diabetic vascular complications is poorly studied. Here, we studied the role of diabetes-induced abnormal endothelial mitochondrial function and the resultant endothelial dysfunction. Understanding the role of endothelial mitochondrial dysfunction in diabetic vasculature is critical in order to develop new therapies. We demonstrate that hyperglycaemia leads to mitochondrial dysfunction in microvascular endothelial cells, and that mitochondrial inhibition induces endothelial dysfunction. Additionally, we show that resveratrol acts as a protective agent; resveratrol-mediated mitochondrial protection may be used to prevent long-term diabetic cardiovascular complications.

  6. Peroxisome Proliferator-Activated Receptors in Female Reproduction and Fertility.

    PubMed

    Vitti, Maurizio; Di Emidio, Giovanna; Di Carlo, Michela; Carta, Gaspare; Antonosante, Andrea; Artini, Paolo Giovanni; Cimini, Annamaria; Tatone, Carla; Benedetti, Elisabetta

    2016-01-01

    Reproductive functions may be altered by the exposure to a multitude of endogenous and exogenous agents, drug or environmental pollutants, which are known to affect gene transcription through the peroxisome proliferator-activated receptors (PPARs) activation. PPARs act as ligand activated transcription factors and regulate metabolic processes such as lipid and glucose metabolism, energy homeostasis, inflammation, and cell proliferation and differentiation. All PPARs isotypes are expressed along the hypothalamic-pituitary-gonadal axis and are strictly involved in reproductive functions. Since female fertility and energy metabolism are tightly interconnected, the research on female infertility points towards the exploration of potential PPARs activating/antagonizing compounds, mainly belonging to the class of thiazolidinediones (TZDs) and fibrates, as useful agents for the maintenance of metabolic homeostasis in women with ovarian dysfunctions. In the present review, we discuss the recent evidence about PPARs expression in the hypothalamic-pituitary-gonadal axis and their involvement in female reproduction. Finally, the therapeutic potential of their manipulation through several drugs is also discussed.

  7. Keeping the Balance Between Proliferation and Differentiation: The Primary Cilium

    PubMed Central

    Irigoín, Florencia; Badano, Jose L

    2011-01-01

    Primary cilia are post-mitotic cellular organelles that are present in the vast majority of cell types in the human body. An extensive body of data gathered in recent years is demonstrating a crucial role for this organelle in a number of cellular processes that include mechano and chemo-sensation as well as the transduction of signaling cascades critical for the development and maintenance of different tissues and organs. Consequently, cilia are currently viewed as cellular antennae playing a critical role at the interphase between cells and their environment, integrating a range of stimuli to modulate cell fate decisions including cell proliferation, migration and differentiation. Importantly, this regulatory role is not just a consequence of their participation in signal transduction but is also the outcome of both the tight synchronization/regulation of ciliogenesis with the cell cycle and the role of individual ciliary proteins in cilia-dependent and independent processes. Here we review the role of primary cilia in the regulation of cell proliferation and differentiation and illustrate how this knowledge has provided insight to understand the phenotypic consequences of ciliary dysfunction. PMID:22131874

  8. Serglycin in Quiescent and Proliferating Primary Endothelial Cells

    PubMed Central

    Reine, Trine M.; Vuong, Tram T.; Rutkovskiy, Arkady; Meen, Astri J.; Vaage, Jarle; Jenssen, Trond G.; Kolset, Svein O.

    2015-01-01

    Proteoglycans are fundamental components of the endothelial barrier, but the functions of the proteoglycan serglycin in endothelium are less described. Our aim was to describe the roles of serglycin in processes relevant for endothelial dysfunction. Primary human umbilical vein endothelial cells (HUVEC) were cultured in vitro and the expression of proteoglycans was investigated. Dense cell cultures representing the quiescent endothelium coating the vasculature was compared to sparse activated cell cultures, relevant for diabetes, cancer and cardiovascular disease. Secretion of 35S- proteoglycans increased in sparse cultures, and we showed that serglycin is a major component of the cell-density sensitive proteoglycan population. In contrast to the other proteoglycans, serglycin expression and secretion was higher in proliferating compared to quiescent HUVEC. RNAi silencing of serglycin inhibited proliferation and wound healing, and serglycin expression and secretion was augmented by hypoxia, mechanical strain and IL-1β induced inflammation. Notably, the secretion of the angiogenic chemokine CCL2 resulting from IL-1β activation, was increased in serglycin knockdown cells, while angiopoietin was not affected. Both serglycin and CCL2 were secreted predominantly to the apical side of polarized HUVEC, and serglycin and CCL2 co-localized both in perinuclear areas and in vesicles. These results suggest functions for serglycin in endothelial cells trough interactions with partner molecules, in biological processes with relevance for diabetic complications, cardiovascular disease and cancer development. PMID:26694746

  9. Peroxisome Proliferator-Activated Receptors in Female Reproduction and Fertility

    PubMed Central

    Carta, Gaspare; Artini, Paolo Giovanni

    2016-01-01

    Reproductive functions may be altered by the exposure to a multitude of endogenous and exogenous agents, drug or environmental pollutants, which are known to affect gene transcription through the peroxisome proliferator-activated receptors (PPARs) activation. PPARs act as ligand activated transcription factors and regulate metabolic processes such as lipid and glucose metabolism, energy homeostasis, inflammation, and cell proliferation and differentiation. All PPARs isotypes are expressed along the hypothalamic-pituitary-gonadal axis and are strictly involved in reproductive functions. Since female fertility and energy metabolism are tightly interconnected, the research on female infertility points towards the exploration of potential PPARs activating/antagonizing compounds, mainly belonging to the class of thiazolidinediones (TZDs) and fibrates, as useful agents for the maintenance of metabolic homeostasis in women with ovarian dysfunctions. In the present review, we discuss the recent evidence about PPARs expression in the hypothalamic-pituitary-gonadal axis and their involvement in female reproduction. Finally, the therapeutic potential of their manipulation through several drugs is also discussed. PMID:27559343

  10. Detection and quantification of intracellular bacterial colonies by automated, high-throughput microscopy.

    PubMed

    Ernstsen, Christina L; Login, Frédéric H; Jensen, Helene H; Nørregaard, Rikke; Møller-Jensen, Jakob; Nejsum, Lene N

    2017-08-01

    To target bacterial pathogens that invade and proliferate inside host cells, it is necessary to design intervention strategies directed against bacterial attachment, cellular invasion and intracellular proliferation. We present an automated microscopy-based, fast, high-throughput method for analyzing size and number of intracellular bacterial colonies in infected tissue culture cells. Cells are seeded in 48-well plates and infected with a GFP-expressing bacterial pathogen. Following gentamicin treatment to remove extracellular pathogens, cells are fixed and cell nuclei stained. This is followed by automated microscopy and subsequent semi-automated spot detection to determine the number of intracellular bacterial colonies, their size distribution, and the average number per host cell. Multiple 48-well plates can be processed sequentially and the procedure can be completed in one working day. As a model we quantified intracellular bacterial colonies formed by uropathogenic Escherichia coli (UPEC) during infection of human kidney cells (HKC-8). Urinary tract infections caused by UPEC are among the most common bacterial infectious diseases in humans. UPEC can colonize tissues of the urinary tract and is responsible for acute, chronic, and recurrent infections. In the bladder, UPEC can form intracellular quiescent reservoirs, thought to be responsible for recurrent infections. In the kidney, UPEC can colonize renal epithelial cells and pass to the blood stream, either via epithelial cell disruption or transcellular passage, to cause sepsis. Intracellular colonies are known to be clonal, originating from single invading UPEC. In our experimental setup, we found UPEC CFT073 intracellular bacterial colonies to be heterogeneous in size and present in nearly one third of the HKC-8 cells. This high-throughput experimental format substantially reduces experimental time and enables fast screening of the intracellular bacterial load and cellular distribution of multiple

  11. Lack of awareness of erectile dysfunction in many men with risk factors for erectile dysfunction

    PubMed Central

    2010-01-01

    Background Men with erectile dysfunction often have concurrent medical conditions. Conversely, men with these conditions may also have underlying erectile dysfunction. The prevalence of unrecognized erectile dysfunction in men with comorbidities commonly associated with erectile dysfunction was determined in men invited to participate in a double-blind, randomized, placebo-controlled trial of sildenafil citrate. Methods Men ≥30 years old presenting with ≥1 erectile dysfunction risk factor (controlled hypertension, hypercholesterolemia, smoking, metabolic syndrome, stable coronary artery disease, diabetes, depression, lower urinary tract symptoms, obesity [body mass index ≥30 kg/m2] or waist circumference ≥40 inches), and not previously diagnosed with erectile dysfunction were evaluated. The screening question, "Do you have erectile dysfunction?," with responses of "no," "yes," and "unsure," and the Erectile Function domain of the International Index of Erectile Function (IIEF-EF) were administered. Results Of 1084 men screened, 1053 answered the screening question and also had IIEF-EF scores. IIEF-EF scores indicating erectile dysfunction occurred in 71% (744/1053), of whom 54% (399/744) had moderate or severe erectile dysfunction. Of 139 answering "yes," 526 answering "unsure," and 388 answering "no," 96%, 90%, and 36%, respectively, had some degree of erectile dysfunction. The mean±SD (range) number of risk factors was 2.9 ± 1.7 (3-8) in the "yes" group, 3.2 ± 1.7 (3-9) in the "unsure" group, and 2.6 ± 1.5 (2-8) in the "no" group. Conclusion Although awareness of having erectile dysfunction was low, most men with risk factors had IIEF-EF scores indicating erectile dysfunction. Erectile dysfunction should be suspected and assessed in men with risk factors, regardless of their apparent level of awareness of erectile dysfunction. Trial registration ClinicalTrials.gov Identifier NCT00343200. PMID:21054874

  12. Gas Centrifuges and Nuclear Proliferation

    SciTech Connect

    Albright, David

    2004-09-15

    Gas centrifuges have been an ideal enrichment method for a wide variety of countries. Many countries have built gas centrifuges to make enriched uranium for peaceful nuclear purposes. Other countries have secretly sought centrifuges to make highly enriched uranium for nuclear weapons. In more recent times, several countries have secretly sought or built gas centrifuges in regions of tension. The main countries that have been of interest in the last two decades have been Pakistan, Iraq, Iran, and North Korea. Currently, most attention is focused on Iran, Pakistan, and North Korea. These states did not have the indigenous abilities to make gas centrifuges, focusing instead on illicit and questionable foreign procurement. The presentation covered the following main sections: Spread of centrifuges through illicit procurement; Role of export controls in stopping proliferation; Increasing the transparency of gas centrifuge programs in non-nuclear weapon states; and, Verified dismantlement of gas centrifuge programs. Gas centrifuges are important providers of low enriched uranium for civil nuclear power reactors. They also pose special nuclear proliferation risks. We all have special responsibilities to prevent the spread of gas centrifuges into regions of tension and to mitigate the consequences of their spread into the Middle East, South Asia, and North Asia.

  13. Negative regulators of cell proliferation

    NASA Technical Reports Server (NTRS)

    Johnson, T. C.; Spooner, B. S. (Principal Investigator)

    1994-01-01

    Cell proliferation is governed by the influence of both mitogens and inhibitors. Although cell contact has long been thought to play a fundamental role in cell cycling regulation, and negative regulators have long been suspected to exist, their isolation and purification has been complicated by a variety of technical difficulties. Nevertheless, over recent years an ever-expanding list of putative negative regulators have emerged. In many cases, their biological inhibitory activities are consistent with density-dependent growth inhibition. Most likely their interactions with mitogenic agents, at an intracellular level, are responsible for either mitotic arrest or continued cell cycling. A review of naturally occurring cell growth inhibitors is presented with an emphasis on those factors shown to be residents of the cell surface membrane. Particular attention is focused on a cell surface sialoglycopeptide, isolated from intact bovine cerebral cortex cells, which has been shown to inhibit the proliferation of an unusually wide range of target cells. The glycopeptide arrest cells obtained from diverse species, both fibroblasts and epithelial cells, and a broad variety of transformed cells. Signal transduction events and a limited spectrum of cells that are refractory to the sialoglycopeptide have provided insight into the molecular events mediated by this cell surface inhibitor.

  14. Erectile dysfunction in COPD patients.

    PubMed

    Turan, Onur; Ure, Iyimser; Turan, Pakize Ayse

    2016-02-01

    Sexual dysfunction is a common problem in chronic obstructive pulmonary disease (COPD). We aimed to assess the presence of erectile dysfunction (ED) in COPD patients. Ninety-three outpatients who had been diagnosed as COPD and followed in Bolvadin State Hospital, Afyon, Turkey, were included in the study. All patients underwent pulmonary function tests and arterial blood gas analysis. They completed International Physical Activity Questionnaire (IPAQ), Medical Research Council (MRC) Dyspnea Scale, Short Form 36-item Scale (SF-36), and International Index of Erectile Function (IIEF) Questionnaire. The mean age of 10 (10.8%) mild, 46 (49.5%) moderate, 28 (30.1%) severe, and 9 (9.7%) very severe COPD patients was 61.4 ± 9.8 years. Varying degrees of ED were detected in 67.7% of COPD patients. All patients with hypoxemia had ED. IPAQ score and all SF-36 parameters were low in patients with ED, while MRC score was high. Forced expiratory volume in one second, forced vital capacity, partial pressure of oxygen in blood, oxygen (O2) saturation, IPAQ score, and role-physical parameters were statistically low in ED patients (p = 0.04, 0.02, <0.01, <0.01, 0.02, and 0.04, respectively); MRC score was statistically higher in patients with ED (p = 0.02). Patients with moderate and severe ED had statistically lower score of mental health (p < 0.01 and p = 0.02, respectively). There was a positive correlation between IIEF score and IPAQ scores (p < 0.01), MRC scores (p = 0.01), general health (p < 0.01), role-physical (p < 0.01), role-emotional (p < 0.01), physical functioning (p < 0.01), and mental health (p < 0.01) parameters in SF-36. ED is frequently seen in COPD patients. Hypoxemia, smoking, and limitation of physical activity are thought to be associated with ED in COPD as mechanisms. Quality of life and the functional capacity are negatively affected with the presence of ED. It is important for a physician to question the sexual functions in patients with COPD. The

  15. NF1 Signal Transduction and Vascular Dysfunction

    DTIC Science & Technology

    2015-05-01

    modulate the mTOR axis. We determined concentrations of metformin , zolendronic acid, and Simvastatin that modulated activation of mTOR as measured by...phosphoS6. Similar to rapamycin, metformin and simvastatin had very modest effects on proliferation of control cells, while zolendronic acid was a...potent inhibitor of all Ras related signaling and proliferation. Metformin was ineffective at inhibiting the proliferation of NF1-kd cells (indeed

  16. Formation of bacterial nanocells

    NASA Astrophysics Data System (ADS)

    Vainshtein, Mikhail; Kudryashova, Ekaterina; Suzina, Natalia; Ariskina, Elena; Voronkov, Vadim

    1998-07-01

    Existence of nanobacteria received increasing attention both in environmental microbiology/geomicro-biology and in medical microbiology. In order to study a production of nanoforms by typical bacterial cells. Effects of different physical factors were investigated. Treatment of bacterial cultures with microwave radiation, or culturing in field of electric current resulted in formation a few types of nanocells. The number and type of nanoforms were determined with type and dose of the treatment. The produced nanoforms were: i) globules, ii) clusters of the globules--probably produced by liaison, iii) nanocells coated with membrane. The viability of the globules is an object opened for doubts. The nanocells discovered multiplication and growth on solidified nutrient media. The authors suggest that formation of nanocells is a common response of bacteria to stress-actions produced by different agents.

  17. Bacterial Cell Wall Components

    NASA Astrophysics Data System (ADS)

    Ginsberg, Cynthia; Brown, Stephanie; Walker, Suzanne

    Bacterial cell-surface polysaccharides cells are surrounded by a variety of cell-surface structures that allow them to thrive in extreme environments. Components of the cell envelope and extracellular matrix are responsible for providing the cells with structural support, mediating intercellular communication, allowing the cells to move or to adhere to surfaces, protecting the cells from attack by antibiotics or the immune system, and facilitating the uptake of nutrients. Some of the most important cell wall components are polysaccharide structures. This review discusses the occurrence, structure, function, and biosynthesis of the most prevalent bacterial cell surface polysaccharides: peptidoglycan, lipopolysaccharide, arabinogalactan, and lipoarabinomannan, and capsular and extracellular polysaccharides. The roles of these polysaccharides in medicine, both as drug targets and as therapeutic agents, are also described.

  18. Bacterial ratchet motors

    PubMed Central

    Di Leonardo, R.; Angelani, L.; Dell’Arciprete, D.; Ruocco, G.; Iebba, V.; Schippa, S.; Conte, M. P.; Mecarini, F.; De Angelis, F.; Di Fabrizio, E.

    2010-01-01

    Self-propelling bacteria are a nanotechnology dream. These unicellular organisms are not just capable of living and reproducing, but they can swim very efficiently, sense the environment, and look for food, all packaged in a body measuring a few microns. Before such perfect machines can be artificially assembled, researchers are beginning to explore new ways to harness bacteria as propelling units for microdevices. Proposed strategies require the careful task of aligning and binding bacterial cells on synthetic surfaces in order to have them work cooperatively. Here we show that asymmetric environments can produce a spontaneous and unidirectional rotation of nanofabricated objects immersed in an active bacterial bath. The propulsion mechanism is provided by the self-assembly of motile Escherichia coli cells along the rotor boundaries. Our results highlight the technological implications of active matter’s ability to overcome the restrictions imposed by the second law of thermodynamics on equilibrium passive fluids. PMID:20457936

  19. Flagella and bacterial pathogenicity.

    PubMed

    Duan, Qiangde; Zhou, Mingxu; Zhu, Liqian; Zhu, Guoqiang

    2013-01-01

    As locomotive organelles, flagella allow bacteria to move toward favorable environments. A flagellum consists of three parts: the basal structure (rotary motor), the hook (universal joint), and the filament (helical propeller). For ages, flagella have been generally regarded as important virulence factors, mainly because of their motility property. However, flagella are getting recognized to play multiple roles with more functions besides motility and chemotaxis. Recent evidence has pinpointed that the bacterial flagella participate in many additional processes including adhesion, biofilm formation, virulence factor secretion, and modulation of the immune system of eukaryotic cells. This mini-review summarizes data from recent studies that elucidated how flagella, as a virulence factor, contribute to bacterial pathogenicity.

  20. Physics of bacterial morphogenesis.

    PubMed

    Sun, Sean X; Jiang, Hongyuan

    2011-12-01

    Bacterial cells utilize three-dimensional (3D) protein assemblies to perform important cellular functions such as growth, division, chemoreception, and motility. These assemblies are composed of mechanoproteins that can mechanically deform and exert force. Sometimes, small-nucleotide hydrolysis is coupled to mechanical deformations. In this review, we describe the general principle for an understanding of the coupling of mechanics with chemistry in mechanochemical systems. We apply this principle to understand bacterial cell shape and morphogenesis and how mechanical forces can influence peptidoglycan cell wall growth. We review a model that can potentially reconcile the growth dynamics of the cell wall with the role of cytoskeletal proteins such as MreB and crescentin. We also review the application of mechanochemical principles to understand the assembly and constriction of the FtsZ ring. A number of potential mechanisms are proposed, and important questions are discussed.

  1. Bacterial Genome Instability

    PubMed Central

    Darmon, Elise

    2014-01-01

    SUMMARY Bacterial genomes are remarkably stable from one generation to the next but are plastic on an evolutionary time scale, substantially shaped by horizontal gene transfer, genome rearrangement, and the activities of mobile DNA elements. This implies the existence of a delicate balance between the maintenance of genome stability and the tolerance of genome instability. In this review, we describe the specialized genetic elements and the endogenous processes that contribute to genome instability. We then discuss the consequences of genome instability at the physiological level, where cells have harnessed instability to mediate phase and antigenic variation, and at the evolutionary level, where horizontal gene transfer has played an important role. Indeed, this ability to share DNA sequences has played a major part in the evolution of life on Earth. The evolutionary plasticity of bacterial genomes, coupled with the vast numbers of bacteria on the planet, substantially limits our ability to control disease. PMID:24600039

  2. [Bacterial diseases of rape].

    PubMed

    Zakharova, O M; Mel'nychuk, M D; Dankevych, L A; Patyka, V P

    2012-01-01

    Bacterial destruction of the culture was described and its agents identified in the spring and winter rape crops. Typical symptoms are the following: browning of stem tissue and its mucilagization, chlorosis of leaves, yellowing and beginning of soft rot in the place of leaf stalks affixion to stems, loss of pigmentation (violet). Pathogenic properties of the collection strains and morphological, cultural, physiological, and biochemical properties of the agents of rape's bacterial diseases isolated by the authors have been investigated. It was found that all the isolates selected by the authors are highly or moderately aggressive towards different varieties of rape. According to the complex of phenotypic properties 44% of the total number of isolates selected by the authors are related to representatives of the genus Pseudomonas, 37% - to Xanthomonas and 19% - to Pectobacterium.

  3. Targeting bacterial toxins.

    PubMed

    Ivarsson, Mattias E; Leroux, Jean-Christophe; Castagner, Bastien

    2012-04-23

    Protein toxins constitute the main virulence factors of several species of bacteria and have proven to be attractive targets for drug development. Lead candidates that target bacterial toxins range from small molecules to polymeric binders, and act at each of the multiple steps in the process of toxin-mediated pathogenicity. Despite recent and significant advances in the field, a rationally designed drug that targets toxins has yet to reach the market. This Review presents the state of the art in bacterial toxin targeted drug development with a critical consideration of achieved breakthroughs and withstanding challenges. The discussion focuses on A-B-type protein toxins secreted by four species of bacteria, namely Clostridium difficile (toxins A and B), Vibrio cholerae (cholera toxin), enterohemorrhagic Escherichia coli (Shiga toxin), and Bacillus anthracis (anthrax toxin), which are the causative agents of diseases for which treatments need to be improved. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Physics of Bacterial Morphogenesis

    PubMed Central

    Sun, Sean X.; Jiang, Hongyuan

    2011-01-01

    Summary: Bacterial cells utilize three-dimensional (3D) protein assemblies to perform important cellular functions such as growth, division, chemoreception, and motility. These assemblies are composed of mechanoproteins that can mechanically deform and exert force. Sometimes, small-nucleotide hydrolysis is coupled to mechanical deformations. In this review, we describe the general principle for an understanding of the coupling of mechanics with chemistry in mechanochemical systems. We apply this principle to understand bacterial cell shape and morphogenesis and how mechanical forces can influence peptidoglycan cell wall growth. We review a model that can potentially reconcile the growth dynamics of the cell wall with the role of cytoskeletal proteins such as MreB and crescentin. We also review the application of mechanochemical principles to understand the assembly and constriction of the FtsZ ring. A number of potential mechanisms are proposed, and important questions are discussed. PMID:22126993

  5. Bacterial transformation of terpenoids

    NASA Astrophysics Data System (ADS)

    Grishko, V. V.; Nogovitsina, Y. M.; Ivshina, I. B.

    2014-04-01

    Data on the bacterial transformation of terpenoids published in the literature in the past decade are analyzed. Possible pathways for chemo-, regio- and stereoselective modifications of terpenoids are discussed. Considerable attention is given to new technological approaches to the synthesis of terpenoid derivatives suitable for the use in the perfume and food industry and promising as drugs and chiral intermediates for fine organic synthesis. The bibliography includes 246 references.

  6. Auditory Dysfunction in Patients with Cerebrovascular Disease

    PubMed Central

    2014-01-01

    Auditory dysfunction is a common clinical symptom that can induce profound effects on the quality of life of those affected. Cerebrovascular disease (CVD) is the most prevalent neurological disorder today, but it has generally been considered a rare cause of auditory dysfunction. However, a substantial proportion of patients with stroke might have auditory dysfunction that has been underestimated due to difficulties with evaluation. The present study reviews relationships between auditory dysfunction and types of CVD including cerebral infarction, intracerebral hemorrhage, subarachnoid hemorrhage, cerebrovascular malformation, moyamoya disease, and superficial siderosis. Recent advances in the etiology, anatomy, and strategies to diagnose and treat these conditions are described. The numbers of patients with CVD accompanied by auditory dysfunction will increase as the population ages. Cerebrovascular diseases often include the auditory system, resulting in various types of auditory dysfunctions, such as unilateral or bilateral deafness, cortical deafness, pure word deafness, auditory agnosia, and auditory hallucinations, some of which are subtle and can only be detected by precise psychoacoustic and electrophysiological testing. The contribution of CVD to auditory dysfunction needs to be understood because CVD can be fatal if overlooked. PMID:25401133

  7. Bacterial nitric oxide synthases.

    PubMed

    Crane, Brian R; Sudhamsu, Jawahar; Patel, Bhumit A

    2010-01-01

    Nitric oxide synthases (NOSs) are multidomain metalloproteins first identified in mammals as being responsible for the synthesis of the wide-spread signaling and protective agent nitric oxide (NO). Over the past 10 years, prokaryotic proteins that are homologous to animal NOSs have been identified and characterized, both in terms of enzymology and biological function. Despite some interesting differences in cofactor utilization and redox partners, the bacterial enzymes are in many ways similar to their mammalian NOS (mNOS) counterparts and, as such, have provided insight into the structural and catalytic properties of the NOS family. In particular, spectroscopic studies of thermostable bacterial NOSs have revealed key oxyheme intermediates involved in the oxidation of substrate L-arginine (Arg) to product NO. The biological functions of some bacterial NOSs have only more recently come to light. These studies disclose new roles for NO in biology, such as taking part in toxin biosynthesis, protection against oxidative stress, and regulation of recovery from radiation damage.

  8. Neglected Bacterial Zoonoses

    PubMed Central

    Chikeka, Ijeuru; Dumler, J. Stephen

    2015-01-01

    Bacterial zoonoses comprise a group of diseases in humans or animals acquired by direct contact with or by oral consumption of contaminated animal materials, or via arthropod vectors. Among neglected infections, bacterial zoonoses are among the most neglected given emerging data on incidence and prevalence as causes of acute febrile illness, even in areas where recognized neglected tropical diseases occur frequently. While many other bacterial infections could also be considered in this neglected category, five distinct infections stand out because they are globally distributed, are acute febrile diseases, have high rates of morbidity and case fatality, and are reported as commonly as malaria, typhoid or dengue virus infections in carefully designed studies in which a broad spectrum diagnoses are actively sought. Thus, this review will focus attention on leptospirosis, relapsing fever borreliosis, and rickettsioses, including scrub typhus, murine typhus and spotted fever group rickettsiosis. Of greatest interest is the lack of distinguishing clinical features among these infections when in humans, which confounds diagnosis where laboratory confirmation is lacking, and in regions where clinical diagnosis is often attributed to one of several perceived more common threats. As diseases such as malaria come under improved control, the real impact of these common and under-recognized infections will become evident, as will the requirement for the strategies and allocation of resources for their control. PMID:25964152

  9. Mangrove bacterial richness

    PubMed Central

    Cleary, Daniel FR; Calado, Ricardo; Costa, Rodrigo

    2011-01-01

    Mangroves are complex and dynamic ecosystems varying in salinity, water level and nutrient availability; they also contain diverse and distinct microbial communities. Studies of microbes and their interactions with other ecosystem components (e.g., tree roots) are critical for our understanding of mangrove ecosystem functioning and remediation. Using a barcoding pyrosequencing approach, we previously noted the persistence of terrestrial bacterial populations on mangrove roots when nursery raised saplings were transplanted back to their natural environment. Here we go into further detail about the potential functional associations of bacterial guilds with distinct mangrove microhabitats including the rhizosphere. We also use a nonparametric richness estimator to show that estimated operational taxonomic unit (OTU) richness is more than twice that observed. In the transplant microhabitat, our estimate suggests that there are almost 7,000 OTU's for a sample size of 10,400 individual sequences with no sign of an asymptote, indicating that “true” richness for this microhabitat is substantially larger. Results on the number of bacterial OTU's should, however, be viewed with caution given that the barcoding pyrosequencing technique used can yield sequencing artifacts that may inflate richness estimates if not properly removed. PMID:21966560

  10. Acute Bacterial Cholangitis

    PubMed Central

    Zimmer, Vincent; Lammert, Frank

    2015-01-01

    Background Acute bacterial cholangitis for the most part owing to common bile duct stones is common in gastroenterology practice and represents a potentially life-threatening condition often characterized by fever, abdominal pain, and jaundice (Charcot's triad) as well as confusion and septic shock (Reynolds' pentad). Methods This review is based on a systematic literature review in PubMed with the search items ‘cholangitis’, ‘choledocholithiasis’, ‘gallstone disease’, ‘biliary infection’, and ‘biliary sepsis’. Results Although most patients respond to empiric broad-spectrum antibiotic treatment, timely endoscopic biliary drainage depending on the severity of the disease is required to eliminate the underlying obstruction. Specific recommendations have been derived from the Tokyo guideline working group consensus 2006 and its update in 2013, albeit poorly evidence-based, providing a comprehensive overview of diagnosis, classification, risk stratification, and treatment algorithms in acute bacterial cholangitis. Conclusion Prompt clinical recognition and accurate diagnostic workup including adequate laboratory assessment and (aetiology-oriented) imaging are critical steps in the management of cholangitis. Treatment is directed at the two major interrelated pathophysiologic components, i.e. bacterial infection (immediate antimicrobial therapy) and bile duct obstruction (biliary drainage). As for the latter, transpapillary endoscopic drainage by stent or nasobiliary drain and/or same-session bile duct clearance, depending on individual disease severity, represent first-line treatment approaches. PMID:26468310

  11. Bacterial infections: uncommon presentations.

    PubMed

    Matz, Hagit; Orion, Edith; Wolf, Ronni

    2005-01-01

    The essence of dermatology is morphology. The most important instrument in the practice of dermatology has always been, and still is, the naked eye; however, "We see only what we are ready to see, what we have been taught to see" (Jean Martin Charcot). Although most practitioners will easily correctly diagnose common bacterial skin diseases (such as cellulitis, erysipelas, impetigo, etc), only a trained and updated dermatologist will recognize the unusual forms and rare variants of these diseases. Bacterial skin diseases are sometimes acute and life-threatening. The mortality rates from necrotizing fasciitis range from 20% to 40%, to name just one example. It is not unreasonable to expect that dermatologists, whether in clinical practice or in referral centers, will be the first physicians to be confronted with unusual variants of bacterial skin diseases that have been unrecognized by non-dermatologists. Some of these cases might even be life-threatening, and only prompt and early recognition, diagnosis, and treatment can make the difference between losing and saving a patient's life. In short, we dermatologists should hone our clinical diagnostic skills and expand our knowledge of the rare forms and unusual and atypical variants of skin diseases: the textbook variants will probably be recognized and treated by general practitioners.

  12. Neglected bacterial zoonoses.

    PubMed

    Chikeka, I; Dumler, J S

    2015-05-01

    Bacterial zoonoses comprise a group of diseases in humans or animals acquired by direct contact with or by oral consumption of contaminated animal materials, or via arthropod vectors. Among neglected infections, bacterial zoonoses are among the most neglected given emerging data on incidence and prevalence as causes of acute febrile illness, even in areas where recognized neglected tropical diseases occur frequently. Although many other bacterial infections could also be considered in this neglected category, five distinct infections stand out because they are globally distributed, are acute febrile diseases, have high rates of morbidity and case fatality, and are reported as commonly as malaria, typhoid or dengue virus infections in carefully designed studies in which broad-spectrum diagnoses are actively sought. This review will focus attention on leptospirosis, relapsing fever borreliosis and rickettsioses, including scrub typhus, murine typhus and spotted fever group rickettsiosis. Of greatest interest is the lack of distinguishing clinical features among these infections when in humans, which confounds diagnosis where laboratory confirmation is lacking, and in regions where clinical diagnosis is often attributed to one of several perceived more common threats. As diseases such as malaria come under improved control, the real impact of these common and under-recognized infections will become evident, as will the requirement for the strategies and allocation of resources for their control. Copyright © 2015 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  13. Different danger signals differently impact on microglial proliferation through alterations of ATP release and extracellular metabolism.

    PubMed

    George, Jimmy; Gonçalves, Francisco Q; Cristóvão, Gonçalo; Rodrigues, Lisa; Meyer Fernandes, José Roberto; Gonçalves, Teresa; Cunha, Rodrigo A; Gomes, Catarina A

    2015-09-01

    Microglia rely on their ability to proliferate in the brain parenchyma to sustain brain innate immunity and participate in the reaction to brain damage. We now studied the influence of different danger signals activating microglia, both internal (typified by glutamate, associated with brain damage) and external (using a bacterial lipopolysaccharide, LPS), on the proliferation of microglia cells. We found that LPS (100 ng/mL) increased, whereas glutamate (0.5 mM) decreased proliferation. Notably, LPS decreased whereas glutamate increased the extracellular levels of ATP. In contrast, LPS increased whereas glutamate decreased the extracellular catabolism of ATP into adenosine through ecto-nucleotidases and ecto-5'-nucleotidase. Finally, apyrase (degrades extracellular ATP) abrogated glutamate-induced inhibition of microglia proliferation; conversely, inhibitors of ecto-nucleotidases (ARL67156 or α,β-methylene ADP) and adenosine deaminase (degrades extracellular adenosine) abrogated the LPS-induced increase of microglia proliferation, which was blocked by a selective A2A receptor antagonist, SCH58261 (50 nM). Overall, these results highlight the importance of the extracellular purinergic metabolism to format microglia proliferation and influence the spatio-temporal profile of neuroinflammation in different conditions of brain damage.

  14. Sarcomere Dysfunction in Nemaline Myopathy

    PubMed Central

    de Winter, Josine M.; Ottenheijm, Coen A.C.

    2017-01-01

    Nemaline myopathy (NM) is among the most common non-dystrophic congenital myopathies (incidence 1:50.000). Hallmark features of NM are skeletal muscle weakness and the presence of nemaline bodies in the muscle fiber. The clinical phenotype of NM patients is quite diverse, ranging from neonatal death to normal lifespan with almost normal motor function. As the respiratory muscles are involved as well, severely affected patients are ventilator-dependent. The mechanisms underlying muscle weakness in NM are currently poorly understood. Therefore, no therapeutic treatment is available yet. Eleven implicated genes have been identified: ten genes encode proteins that are either components of thin filament, or are thought to contribute to stability or turnover of thin filament proteins. The thin filament is a major constituent of the sarcomere, the smallest contractile unit in muscle. It is at this level of contraction – thin-thick filament interaction – where muscle weakness originates in NM patients. This review focusses on how sarcomeric gene mutations directly compromise sarcomere function in NM. Insight into the contribution of sarcomeric dysfunction to muscle weakness in NM, across the genes involved, will direct towards the development of targeted therapeutic strategies. PMID:28436394

  15. Sarcomere Dysfunction in Nemaline Myopathy.

    PubMed

    de Winter, Josine M; Ottenheijm, Coen A C

    2017-01-01

    Nemaline myopathy (NM) is among the most common non-dystrophic congenital myopathies (incidence 1:50.000). Hallmark features of NM are skeletal muscle weakness and the presence of nemaline bodies in the muscle fiber. The clinical phenotype of NM patients is quite diverse, ranging from neonatal death to normal lifespan with almost normal motor function. As the respiratory muscles are involved as well, severely affected patients are ventilator-dependent. The mechanisms underlying muscle weakness in NM are currently poorly understood. Therefore, no therapeutic treatment is available yet.Eleven implicated genes have been identified: ten genes encode proteins that are either components of thin filament, or are thought to contribute to stability or turnover of thin filament proteins. The thin filament is a major constituent of the sarcomere, the smallest contractile unit in muscle. It is at this level of contraction - thin-thick filament interaction - where muscle weakness originates in NM patients.This review focusses on how sarcomeric gene mutations directly compromise sarcomere function in NM. Insight into the contribution of sarcomeric dysfunction to muscle weakness in NM, across the genes involved, will direct towards the development of targeted therapeutic strategies.

  16. Mitochondrial mechanisms of endothelial dysfunction.

    PubMed

    Szewczyk, Adam; Jarmuszkiewicz, Wieslawa; Koziel, Agnieszka; Sobieraj, Izabela; Nobik, Wioletta; Lukasiak, Agnieszka; Skup, Agata; Bednarczyk, Piotr; Drabarek, Beata; Dymkowska, Dorota; Wrzosek, Antoni; Zablocki, Krzysztof

    2015-08-01

    Endothelial cells play an important physiological role in vascular homeostasis. They are also the first barrier that separates blood from deeper layers of blood vessels and extravascular tissues. Thus, they are exposed to various physiological blood components as well as challenged by pathological stimuli, which may exert harmful effects on the vascular system by stimulation of excessive generation of reactive oxygen species (ROS). The major sources of ROS are NADPH oxidase and mitochondrial respiratory chain complexes. Modulation of mitochondrial energy metabolism in endothelial cells is thought to be a promising target for therapy in various cardiovascular diseases. Uncoupling protein 2 (UCP2) is a regulator of mitochondrial ROS generation and can antagonise oxidative stress-induced endothelial dysfunction. Several studies have revealed the important role of UCP2 in hyperglycaemia-induced modifications of mitochondrial function in endothelial cells. Additionally, potassium fluxes through the inner mitochondrial membrane, which are involved in ROS synthesis, affect the mitochondrial volume and change both the mitochondrial membrane potential and the transport of calcium into the mitochondria. In this review, we concentrate on the mitochondrial role in the cytoprotection phenomena of endothelial cells. Copyright © 2015 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  17. The anatomy of group dysfunction.

    PubMed

    Hayes, David F

    2014-04-01

    The dysfunction of the radiology group has 2 components: (1) the thinking component-the governance structure of the radiology group; how we manage the group; and (2) the structural component-the group's business model and its conflict with the partner's personal business model. Of the 2 components, governance is more important. Governance must be structured on classic, immutable business management principles. The structural component, the business model, is not immutable. In fact, it must continually change in response to the marketplace. Changes in the business model should occur only if demanded or permitted by the marketplace; instituting changes for other reasons, including personal interests or deficient knowledge of the deciders, is fundamentally contrary to the long-term interests of the group and its owners. First, we must learn basic business management concepts to appreciate the function and necessity of standard business models and standard business governance. Peter Drucker's The Effective Executive is an excellent primer on the subjects of standard business practices and the importance of a functional, authorized, and fully accountable chief executive officer.

  18. Erectile dysfunction in multiple sclerosis.

    PubMed

    Kirkeby, H J; Poulsen, E U; Petersen, T; Dørup, J

    1988-09-01

    In a sample of 29 impotent men with multiple sclerosis and erectile problems, penile arterial inflow and venous outflow were within normal limits. In 26 patients, the pudendal evoked potential (PEP) was abnormal, and eight of these also had abnormal bulbocavernous reflex (BCR). Three patients had abnormal PEP and normal BCR, and of these, two had normal and one had abnormal nocturnal erectile activity. The validity of PEP/BCR testing was supported by normal findings in six patients with MS and without erectile problems. Nocturnal erectile activity was normal in 11 patients, of whom nine had abnormal PEP and/or BCR. A high disability score corresponded poorly with both reduced sexual function, insufficient nocturnal erectile activity, and abnormal PEP and/or BCR. Intracavernous injection of papaverine gave erection in 27 patients, the dose needed to create an erection being inversely related to the level of disablement. PEP and BCR testing may be more sensitive in defining neurogenic erectile dysfunction (ED) than nocturnal erectile activity. We considered 26 of the cases to have a neurogenic cause of ED and three to have mainly a psychogenic cause.

  19. Polyphenols in preventing endothelial dysfunction.

    PubMed

    Biegańska-Hensoldt, Sylwia; Rosołowska-Huszcz, Danuta

    2017-03-27

    One of the main causes of mortality in developed countries is atherosclerosis. The pathogenesis of atherosclerosis is associated with endothelial dysfunction. Consumption of food rich in natural antioxidants including polyphenols significantly improves endothelial cells functions. Polyphenols have a beneficial effect on the human body and play an important part in protecting the cardiovascular system. Polyphenols present in food have antioxidant, anti-inflammatory, antihypertensive, antithrombotic and antiproliferative properties. Catechins cause an increase in the activity of endothelial nitric oxide synthase (eNOS) and increased production of nitric oxide (NO) and decrease in blood pressure. Catechins also reduce platelet adhesion, lower the concentration of C-reactive protein and tumor necrosis factor alpha and interleukin-6. Resveratrol inhibits NADPH oxidase expression, increases the expression of eNOS and NO production as well as decreases the expression of proinflammatory cytokines, and also lowers the concentration of the soluble forms of adhesion molecules - sICAM-1 and sVCAM-1 in blood. Quercetin reduces the blood level of low density lipoprotein cholesterol, lowers blood pressure, reduces the concentration of C-reactive protein and F2-isoprostane level. Curcumin has antagonistic activity to homocysteine. Curcumin increases the expression of eNOS and reduces oxidative DNA damage in rat cardiomyocytes. Numerous attempts are taken for improving the bioavailability of polyphenols in order to increase their use in the body.

  20. Diaphragmatic Dysfunction after Thoracic Operations.

    PubMed

    Gaissert, Henning; Wilcox, Susan R

    2016-12-01

    The perioperative management of diaphragmatic weakness and phrenic nerve dysfunction is complex, due to varied etiologies and clinical presentations. The factors leading to diaphragmatic weakness may culminate after the operation with transient or persistent respiratory failure. This review discusses diaphragmatic disorders and postoperative respiratory failure caused by unilateral or bilateral diaphragmatic impairment. The origins of neuromuscular weakness involving the diaphragm are diverse, and often lie within the domains of different medical specialties, with only a portion of the condition related to surgical intervention. Consideration of underlying etiologies for any individual patient requires thorough multidisciplinary review. The most important clinical scenarios compounding diaphragmatic weakness, including acute myasthenic states, persistent neuromuscular blockade, and surgical injury to the phrenic nerve or diaphragm, are accessible to attentive surgeons. Awareness of the signs and symptoms of undiagnosed weakness, preoperative pursuit of its diagnosis, knowledge of surgical alternatives to phrenic nerve resection, and cooperative skills in the multidisciplinary management of myasthenia all are crucial to improve patient outcomes. Georg Thieme Verlag KG Stuttgart · New York.

  1. Repairing Mitochondrial Dysfunction in Disease.

    PubMed

    Sorrentino, Vincenzo; Menzies, Keir J; Auwerx, Johan

    2017-09-27

    Mitochondria are essential organelles for many aspects of cellular homeostasis, including energy harvesting through oxidative phosphorylation. Alterations of mitochondrial function not only impact on cellular metabolism but also critically influence whole-body metabolism, health, and life span. Diseases defined by mitochondrial dysfunction have also expanded from rare monogenic disorders in a strict sense to now also include many common polygenic diseases, including metabolic, cardiovascular, neurodegenerative, and neuromuscular diseases. This has led to an intensive search for new therapeutic and preventive strategies aimed at invigorating mitochondrial function by exploiting key components of mitochondrial biogenesis, redox metabolism, dynamics, mitophagy, and the mitochondrial unfolded protein response. As such, new findings linking mitochondrial function to the progression or outcome of this ever-increasing list of diseases has stimulated the discovery and development of the first true mitochondrial drugs, which are now entering the clinic and are discussed in this review. Expected final online publication date for the Annual Review of Pharmacology and Toxicology Volume 58 is January 6, 2018. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

  2. Diastolic dysfunction in arterial hypertension.

    PubMed

    de Simone, G; Palmieri, V

    2001-01-01

    Left ventricular diastolic properties are important markers of pump function and are frequently abnormal when myocardial insults alter tissue structure. Alterations can be limited to the early diastolic phase (early active relaxation) or to late diastolic filling (late ventricular compliance), but more often involve regulation of both phases of diastole. In asymptomatic patients with arterial hypertension, left ventricular relaxation is often prolonged, independently, at least in part, of cardiac loading conditions and left ventricular geometry, but this abnormality is associated with early signs of systolic dysfunction. Uncontrolled hypertension, diabetes, and obesity are most often associated with ischemic heart disease and impaired diastolic function. Reducing blood pressure with antihypertension therapy will reduce myocardial afterload, regress LVH, and improve systolic and diastolic function. In patients with symptoms of CHF with a normal ejection fraction, however, changes in therapy may be indicated. Greater emphasis should be placed on using medications that decrease myocardial load, but also reduce the effects of neurohormonal activation. (c)2001 by Le Jacq Communications, Inc.

  3. Mitochondrial dysfunction in neuromuscular disorders.

    PubMed

    Katsetos, Christos D; Koutzaki, Sirma; Melvin, Joseph J

    2013-09-01

    This review deciphers aspects of mitochondrial (mt) dysfunction among nosologically, pathologically, and genetically diverse diseases of the skeletal muscle, lower motor neuron, and peripheral nerve, which fall outside the traditional realm of mt cytopathies. Special emphasis is given to well-characterized mt abnormalities in collagen VI myopathies (Ullrich congenital muscular dystrophy and Bethlem myopathy), megaconial congenital muscular dystrophy, limb-girdle muscular dystrophy type 2 (calpainopathy), centronuclear myopathies, core myopathies, inflammatory myopathies, spinal muscular atrophy, Charcot-Marie-Tooth neuropathy type 2, and drug-induced peripheral neuropathies. Among inflammatory myopathies, mt abnormalities are more prominent in inclusion body myositis and a subset of polymyositis with mt pathology, both of which are refractory to corticosteroid treatment. Awareness is raised about instances of phenotypic mimicry between cases harboring primary mtDNA depletion, in the context of mtDNA depletion syndrome, and established neuromuscular disorders such as spinal muscular atrophy. A substantial body of experimental work, derived from animal models, attests to a major role of mitochondria (mt) in the early process of muscle degeneration. Common mechanisms of mt-related cell injury include dysregulation of the mt permeability transition pore opening and defective autophagy. The therapeutic use of mt permeability transition pore modifiers holds promise in various neuromuscular disorders, including muscular dystrophies.

  4. Tumor-induced immune dysfunction.

    PubMed

    Kiessling, R; Wasserman, K; Horiguchi, S; Kono, K; Sjöberg, J; Pisa, P; Petersson, M

    1999-10-01

    Immune system-based approaches for the treatment of malignant disease over the past decades have often focused on cytolytic effector cells such as cytotoxic T lymphocytes (CTL), and natural killer (NK) cells. It has also been demonstrated that tumor-bearing mice can be cured using a wide variety of approaches, some of which involve cytokine-mediated enhancement of CTL and NK cell activity. However, the apparent success in mice stands in contrast to the current situation in the clinic, wherein only a minority of patients have thus far benefited from CTL- or NK cell-based antitumor approaches. The underlying causes of tumor-associated immune suppression of CTL and NK cell activity are discussed, and features of interest shared with HIV infection, leprosy, and rheumatoid arthritis are also be mentioned. Remarkable and very recent observations have shed more light upon the causes of dysfunctional alterations in CTL and NK cells often associated with these diseases, that in turn have suggested new immunotherapeutic approaches for cancer and infectious disease.

  5. Radiation hepatology of the rat: The effects of the proliferation stimulus induced by subtotal hepatectomy

    SciTech Connect

    Geraci, J.P.; Mariano, M.S.

    1994-11-01

    The effect of an 80 to 90% hepatectomy in stimulating proliferation immediately after irradiation of the liver was studied. A dose of 15 Gy was not lethal for animals with intact livers, but all animals with subtotal hepatectomies exposed to this dose died from apparent liver failure 28 to 60 days after exposure. To elucidate the mechanism for this mortality, plasma aspartate aminotransferase, retention of intravenous injected rose bengal, liver weight and liver hydroxyproline content were measured 0 to 90 days after 15 Gy irradiation of the liver to determine temporal changes in necrosis, function, mass and fibrosis, respectively, in animals with either intact livers or livers with subtotal resection. Irradiation of the liver had no significant effect on these parameters in animals with intact livers. In subtotally hepatectomized animals the same radiation dose that suppressed liver mass restoration significantly increased hepatocyte necrosis within 7 days, which was followed by increased liver hydroxyproline concentration and hepatic dysfunction. This radiation-induced temporal change in hepatic dysfunction correlated with increased concentration of hydroxyproline but not with liver mass, indicating that liver fibrosis was the cause of hepatic dysfunction. Since similar sequelae are produced in intact livers after higher doses and longer intervals after irradiation, the proliferation stimulus induced by partial hepatectomy must accelerate the expression of damage and lower the radiation tolerance of the liver. However, in subtotally hepatectomized animals radiation-induced hepatocyte necrosis precedes fibrosis, whereas the reverse is normally true for animals with intact livers. 35 refs., 5 figs.

  6. Management of Chronic Spinal Cord Dysfunction

    PubMed Central

    Abrams, Gary M.; Ganguly, Karunesh

    2015-01-01

    Purpose of Review: Both acute and chronic spinal cord disorders present multisystem management problems to the clinician. This article highlights key issues associated with chronic spinal cord dysfunction. Recent Findings: Advances in symptomatic management for chronic spinal cord dysfunction include use of botulinum toxin to manage detrusor hyperreflexia, pregabalin for management of neuropathic pain, and intensive locomotor training for improved walking ability in incomplete spinal cord injuries. Summary: The care of spinal cord dysfunction has advanced significantly over the past 2 decades. Management and treatment of neurologic and non-neurologic complications of chronic myelopathies ensure that each patient will be able to maximize their functional independence and quality of life. PMID:25651225

  7. [Management of autonomic dysfunction in Parkinson's disease].

    PubMed

    Crespo-Burillo, José A; Alarcia-Alejos, Raquel

    2015-04-16

    Autonomic dysfunction is a common manifestation in patients with in Parkinson's disease, which can sometimes precede motor impairment. It can be expressed as orthostatic and postprandial hypotension, supine hypertension, hypersalivation, constipation, delayed gastric emptying, dyshidrosis, bladder and sexual dysfunction. It impairs the quality of life of patients and complicates the management of motor symptoms. Evidence available to treat complications is low. Our aim is to review the pathophysiology and clinical features of autonomic dysfunction in Parkinson's disease and provide a practical approach to handling the available evidence.

  8. Velo-pharyngeal dysfunction: Evaluation and management

    PubMed Central

    Marsh, Jeffrey L.

    2009-01-01

    Separation of the nasal and oral cavities by dynamic closure of the velo-pharyngeal port is necessary for normal speech and swallowing. Velo-pharyngeal dysfunction (VPD) may either follow repair of a cleft palate or be independent of clefting. While the diagnosis of VPD is made by audiologic perceptual evaluation of speech, identification of the mechanism of the dysfunction requires instrumental visualization of the velo-pharyngeal port during specific speech tasks. Matching the specific intervention for management of VPD with the type of dysfunction, i.e. differential management for differential diagnosis, maximizes the result while minimizing the morbidity of the intervention. PMID:19884668

  9. Male Sexual Dysfunction and Chronic Kidney Disease

    PubMed Central

    Edey, Matthew M.

    2017-01-01

    Male sexual dysfunction is common in chronic kidney disease (CKD), particularly in end-stage renal disease. Historically, this cause of considerable morbidity has been under-reported and under-recognized. The ideal approach to diagnosis and management remains unclear due to a paucity of good quality data, but an understanding of the pathophysiology is necessary in order to address the burden of this important complication of CKD. This paper will review the endocrine dysfunction that occurs in renal disease, particularly the hypothalamic–pituitary–gonadal axis, discuss the causes of erectile dysfunction, infertility, and altered body image and libido in these patients and suggest appropriate treatment interventions. PMID:28382300

  10. Sexual dysfunction within an adult developmental perspective.

    PubMed

    Fagan, P J; Meyer, J K; Schmidt, C W

    1986-01-01

    The focus of this paper is on the adult who has adequately mastered the oedipal stage of psychosexual development and who presents with a sexual dysfunction. Drawing on the developmental sequence of Erik Erikson, the authors suggest that failure to address adequately an adult psychosocial crisis may result in sexual dysfunction. There may be both adult developmental deficits and regression to adolescent and adult stages previously negotiated. Both may be symptomatically represented by sexual dysfunction. The authors urge that the sexual and marital problems be evaluated within an adult developmental framework and that the therapy address the psychosocial issues which are appropriate to the developmental stage of the patient.

  11. Dysfunctions of micturition in the male.

    PubMed

    Smucker, D R; Zilkoski, M W; Jhunjhunwala, J

    1989-12-01

    A basic knowledge of the anatomy and neurophysiology of the lower urinary tract is necessary to understand voiding dysfunction in the male. Enuresis is the most common voiding problem in children. Evaluation and treatment of incontinence and neurogenic voiding dysfunction in the adult male is easily understood by using a failure to store/failure to empty classification system. Treatment focuses on behavioral, pharmacologic, and surgical means of influencing the storage and emptying functions of the bladder and sphincter. The goals of any treatment plan for dysfunctions of micturition in the male are to preserve renal function, maintain continence, and promote normal voiding patterns.

  12. Data for automated, high-throughput microscopy analysis of intracellular bacterial colonies using spot detection.

    PubMed

    Ernstsen, Christina L; Login, Frédéric H; Jensen, Helene H; Nørregaard, Rikke; Møller-Jensen, Jakob; Nejsum, Lene N

    2017-10-01

    Quantification of intracellular bacterial colonies is useful in strategies directed against bacterial attachment, subsequent cellular invasion and intracellular proliferation. An automated, high-throughput microscopy-method was established to quantify the number and size of intracellular bacterial colonies in infected host cells (Detection and quantification of intracellular bacterial colonies by automated, high-throughput microscopy, Ernstsen et al., 2017 [1]). The infected cells were imaged with a 10× objective and number of intracellular bacterial colonies, their size distribution and the number of cell nuclei were automatically quantified using a spot detection-tool. The spot detection-output was exported to Excel, where data analysis was performed. In this article, micrographs and spot detection data are made available to facilitate implementation of the method.

  13. Collective chemotaxis and segregation of active bacterial colonies

    PubMed Central

    Amar, M. Ben

    2016-01-01

    Still recently, bacterial fluid suspensions have motivated a lot of works, both experimental and theoretical, with the objective to understand their collective dynamics from universal and simple rules. Since some species are active, most of these works concern the strong interactions that these bacteria exert on a forced flow leading to instabilities, chaos and turbulence. Here, we investigate the self-organization of expanding bacterial colonies under chemotaxis, proliferation and eventually active-reaction. We propose a simple model to understand and quantify the physical properties of these living organisms which either give cohesion or on the contrary dispersion to the colony. Taking into account the diffusion and capture of morphogens complicates the model since it induces a bacterial density gradient coupled to bacterial density fluctuations and dynamics. Nevertheless under some specific conditions, it is possible to investigate the pattern formation as a usual viscous fingering instability. This explains the similarity and differences of patterns according to the physical bacterial suspension properties and explain the factors which favor compactness or branching. PMID:26888040

  14. Collective chemotaxis and segregation of active bacterial colonies.

    PubMed

    Ben Amar, M

    2016-02-18

    Still recently, bacterial fluid suspensions have motivated a lot of works, both experimental and theoretical, with the objective to understand their collective dynamics from universal and simple rules. Since some species are active, most of these works concern the strong interactions that these bacteria exert on a forced flow leading to instabilities, chaos and turbulence. Here, we investigate the self-organization of expanding bacterial colonies under chemotaxis, proliferation and eventually active-reaction. We propose a simple model to understand and quantify the physical properties of these living organisms which either give cohesion or on the contrary dispersion to the colony. Taking into account the diffusion and capture of morphogens complicates the model since it induces a bacterial density gradient coupled to bacterial density fluctuations and dynamics. Nevertheless under some specific conditions, it is possible to investigate the pattern formation as a usual viscous fingering instability. This explains the similarity and differences of patterns according to the physical bacterial suspension properties and explain the factors which favor compactness or branching.

  15. The development of permafrost bacterial communities under submarine conditions

    NASA Astrophysics Data System (ADS)

    Mitzscherling, Julia; Winkel, Matthias; Winterfeld, Maria; Horn, Fabian; Yang, Sizhong; Grigoriev, Mikhail N.; Wagner, Dirk; Overduin, Pier P.; Liebner, Susanne

    2017-07-01

    Submarine permafrost is more vulnerable to thawing than permafrost on land. Besides increased heat transfer from the ocean water, the penetration of salt lowers the freezing temperature and accelerates permafrost degradation. Microbial communities in thawing permafrost are expected to be stimulated by warming, but how they develop under submarine conditions is completely unknown. We used the unique records of two submarine permafrost cores from the Laptev Sea on the East Siberian Arctic Shelf, inundated about 540 and 2500 years ago, to trace how bacterial communities develop depending on duration of the marine influence and pore water chemistry. Combined with geochemical analysis, we quantified total cell numbers and bacterial gene copies and determined the community structure of bacteria using deep sequencing of the bacterial 16S rRNA gene. We show that submarine permafrost is an extreme habitat for microbial life deep below the seafloor with changing thermal and chemical conditions. Pore water chemistry revealed different pore water units reflecting the degree of marine influence and stages of permafrost thaw. Millennia after inundation by seawater, bacteria stratify into communities in permafrost, marine-affected permafrost, and seabed sediments. In contrast to pore water chemistry, the development of bacterial community structure, diversity, and abundance in submarine permafrost appears site specific, showing that both sedimentation and permafrost thaw histories strongly affect bacteria. Finally, highest microbial abundance was observed in the ice-bonded seawater unaffected but warmed permafrost of the longer inundated core, suggesting that permafrost bacterial communities exposed to submarine conditions start to proliferate millennia after warming.

  16. TBK1 Protects Vacuolar Integrity during Intracellular Bacterial Infection

    PubMed Central

    Radtke, Andrea L; Delbridge, Laura M; Balachandran, Siddharth; Barber, Glen N; O'Riordan, Mary X. D

    2007-01-01

    TANK-binding kinase-1 (TBK1) is an integral component of Type I interferon induction by microbial infection. The importance of TBK1 and Type I interferon in antiviral immunity is well established, but the function of TBK1 in bacterial infection is unclear. Upon infection of murine embryonic fibroblasts with Salmonella enterica serovar Typhimurium (Salmonella), more extensive bacterial proliferation was observed in tbk1−/− than tbk1+/+ cells. TBK1 kinase activity was required for restriction of bacterial infection, but interferon regulatory factor-3 or Type I interferon did not contribute to this TBK1-dependent function. In tbk1−/−cells, Salmonella, enteropathogenic Escherichia coli, and Streptococcus pyogenes escaped from vacuoles into the cytosol where increased replication occurred, which suggests that TBK1 regulates the integrity of pathogen-containing vacuoles. Knockdown of tbk1 in macrophages and epithelial cells also resulted in increased bacterial localization in the cytosol, indicating that the role of TBK1 in maintaining vacuolar integrity is relevant in different cell types. Taken together, these data demonstrate a requirement for TBK1 in control of bacterial infection distinct from its established role in antiviral immunity. PMID:17335348

  17. Collective chemotaxis and segregation of active bacterial colonies

    NASA Astrophysics Data System (ADS)

    Amar, M. Ben

    2016-02-01

    Still recently, bacterial fluid suspensions have motivated a lot of works, both experimental and theoretical, with the objective to understand their collective dynamics from universal and simple rules. Since some species are active, most of these works concern the strong interactions that these bacteria exert on a forced flow leading to instabilities, chaos and turbulence. Here, we investigate the self-organization of expanding bacterial colonies under chemotaxis, proliferation and eventually active-reaction. We propose a simple model to understand and quantify the physical properties of these living organisms which either give cohesion or on the contrary dispersion to the colony. Taking into account the diffusion and capture of morphogens complicates the model since it induces a bacterial density gradient coupled to bacterial density fluctuations and dynamics. Nevertheless under some specific conditions, it is possible to investigate the pattern formation as a usual viscous fingering instability. This explains the similarity and differences of patterns according to the physical bacterial suspension properties and explain the factors which favor compactness or branching.

  18. Expression of bacterial genes in plant cells.

    PubMed Central

    Fraley, R T; Rogers, S G; Horsch, R B; Sanders, P R; Flick, J S; Adams, S P; Bittner, M L; Brand, L A; Fink, C L; Fry, J S; Galluppi, G R; Goldberg, S B; Hoffmann, N L; Woo, S C

    1983-01-01

    Chimeric bacterial genes conferring resistance to aminoglycoside antibiotics have been inserted into the Agrobacterium tumefaciens tumor-inducing (Ti) plasmid and introduced into plant cells by in vitro transformation techniques. The chimeric genes contain the nopaline synthase 5' and 3' regulatory regions joined to the genes for neomycin phosphotransferase type I or type II. The chimeric genes were cloned into an intermediate vector, pMON120, and inserted into pTiB6S3 by recombination and then introduced into petunia and tobacco cells by cocultivating A. tumefaciens cells with protoplast-derived cells. Southern hybridization was used to confirm the presence of the chimeric genes in the transformed plant tissues. Expression of the chimeric genes was determined by the ability of the transformed cells to proliferate on medium containing normally inhibitory levels of kanamycin (50 micrograms/ml) or other aminoglycoside antibiotics. Plant cells transformed by wild-type pTiB6S3 or derivatives carrying the bacterial neomycin phosphotransferase genes with their own promoters failed to grow under these conditions. The significance of these results for plant genetic engineering is discussed. Images PMID:6308651

  19. Chronic Inhibition of PPAR-γ Signaling Induces Endothelial Dysfunction In The Juvenile Lamb

    PubMed Central

    Sharma, Shruti; Barton, Jubilee; Rafikov, Ruslan; Aggarwal, Saurabh; Kuo, Hsuan-Chang; Oishi, Peter E.; Datar, Sanjeev A.; Fineman, Jeffrey R; Black, Stephen M.

    2013-01-01

    We have recently shown that the development of endothelial dysfunction in lambs with increased pulmonary blood flow (PBF) correlates with a decrease in peroxisome proliferator activated receptor-γ (PPAR-γ) signaling. Thus, in this study we determined if the loss of PPAR-γ signaling is necessary and sufficient to induce endothelial dysfunction by exposing lambs with normal PBF to the PPAR-γ antagonist, GW9662. Two-weeks of exposure to GW9662 significantly decreased both PPAR-γ protein and activity. In addition, although eNOS protein and nitric oxide metabolites (NOx) were significantly increased, endothelial dependent pulmonary vasodilation in response to acetylcholine was attenuated, indicative of endothelial dysfunction. To elucidate whether downstream mediators of vasodilation were impaired we examined soluble guanylate cyclase (sGC)- α and β subunit protein, cGMP levels, and phosphodiesterase 5 (PDE5) protein and activity, but we found no significant changes. However, we found that peroxynitrite levels were significantly increased in GW9662-treated lambs and this correlated with a significant increase in protein kinase G-1α (PKG-1α) nitration and a reduction in PKG activity. Peroxynitrite is formed by the interaction of NO with superoxide and we found that there was a significant increase in superoxide generation in GW9662-treated lambs. Further, we identified dysfunctional mitochondria as the primary source of the increased superoxide. Finally, we found that the mitochondrial dysfunction was due to a disruption in carnitine metabolism. We conclude that loss of PPAR-γ signaling is sufficient to induce endothelial dysfunction confirming its important role in maintaining a healthy vasculature. PMID:23257346

  20. Cell proliferation in normal epidermis

    SciTech Connect

    Weinstein, G.D.; McCullough, J.L.; Ross, P.

    1984-06-01

    A detailed examination of cell proliferation kinetics in normal human epidermis is presented. Using tritiated thymidine with autoradiographic techniques, proliferative and differentiated cell kinetics are defined and interrelated. The proliferative compartment of normal epidermis has a cell cycle duration (Tc) of 311 h derived from 3 components: the germinative labeling index (LI), the duration of DNA synthesis (ts), and the growth fraction (GF). The germinative LI is 2.7% +/- 1.2 and ts is 14 h, the latter obtained from a composite fraction of labeled mitoses curve obtained from 11 normal subjects. The GF obtained from the literature and from human skin xenografts to nude mice is estimated to be 60%. Normal-appearing epidermis from patients with psoriasis appears to have a higher proliferation rate. The mean LI is 4.2% +/- 0.9, approximately 50% greater than in normal epidermis. Absolute cell kinetic values for this tissue, however, cannot yet be calculated for lack of other information on ts and GF. A kinetic model for epidermal cell renewal in normal epidermis is described that interrelates the rate of birth/entry, transit, and/or loss of keratinocytes in the 3 epidermal compartments: proliferative, viable differentiated (stratum malpighii), and stratum corneum. Expected kinetic homeostasis in the epidermis is confirmed by the very similar ''turnover'' rates in each of the compartments that are, respectively, 1246, 1417, and 1490 cells/day/mm2 surface area. The mean epidermal turnover time of the entire tissue is 39 days. The Tc of 311 h in normal cells in 8-fold longer than the psoriatic Tc of 36 h and is necessary for understanding the hyperproliferative pathophysiologic process in psoriasis.

  1. Dietary modulation of peroxisome proliferator-activated receptor gamma.

    PubMed

    Marion-Letellier, R; Déchelotte, P; Iacucci, M; Ghosh, S

    2009-04-01

    Peroxisome proliferator-activated receptor gamma (PPAR gamma) is a nuclear receptor that regulates intestinal inflammation. PPAR gamma is highly expressed in the colon and can be activated by various dietary ligands. A number of fatty acids such as polyunsaturated fatty acids or eicosanoids are considered as endogenous PPAR gamma activators. Nevertheless, other nutrients such as glutamine, spicy food or flavonoids are also able to activate PPAR gamma. As PPAR gamma plays a key role in bacterial induced inflammation, anti-inflammatory properties of probiotics may be mediated through PPAR gamma. The aims of the present review are to discuss of the potential roles of dietary compounds in modulating intestinal inflammation through PPAR gamma.

  2. Proliferation resistance: issues, initiatives and evaluation

    SciTech Connect

    Pilat, Joseph F

    2009-01-01

    The vision of a nuclear renaissance has highlighted the issue of proliferation resistance. The prospects for a dramatic growth in nuclear power may depend on the effectiveness of, and the resources devoted to, plans to develop and implement technologies and approaches that strengthen proliferation resistance. The GenIV International Forum (GIF) and others have devoted attention and resources to proliferation resistance. However, the hope of finding a way to make the peaceful uses of nuclear energy resistant to proliferation has reappeared again and again in the history of nuclear power with little practical consequence. The concept of proliferation resistance has usually focused on intrinsic (technological) as opposed to extrinsic (institutional) factors. However, if there are benefits that may yet be realized from reactors and other facilities designed to minimize proliferation risks, it is their coupling with effective safeguards and other nonproliferation measures that likely will be critical. Proliferation resistance has also traditionally been applied only to state threats. Although there are no technologies that can wholly eliminate the risk of proliferation by a determined state, technology can play a limited role in reducing state threats and perhaps in eliminating many non-state threats. These and other issues are not academic. They affect efforts to evaluate proliferation resistance, including the methodology developed by GIF's Proliferation Resistance and Physical Protection (PR&PP) Working Group as well as the proliferation resistance initiatives that are being pursued or may be developed in the future. This paper will offer a new framework for thinking about proliferation resistance issues, including the ways the output of the methodology could be developed to inform the decisions that states, the International Atomic Energy (IAEA) and others will have to make in order to fully realize the promise of a nuclear renaissance.

  3. Cell Proliferation, Cell Death, and Size Regulation

    DTIC Science & Technology

    1998-10-01

    Cell Death , and Size Regulation PRINCIPAL INVESTIGATOR: Nicholas E. Baker, Ph.D. CONTRACTING ORGANIZATION: Albert Einstein College of Medicine of Yeshiva...SUBTITLE 5. FUNDING NUMBERS Cell Proliferation, Cell Death , and Size Regulation DAMD17-97-1-7034 6. AUTHOR(S) Nicholas E. Baker, Ph.D. 7. PERFORMING...Contains unpublished data 5 CELL PROLIFERATION, CELL DEATH , AND SIZE REGULATION INTRODUCTION Cell proliferation and cell death come to attention through

  4. Stratum corneum dysfunction in dandruff.

    PubMed

    Turner, G A; Hoptroff, M; Harding, C R

    2012-08-01

    Dandruff is characterized by a flaky, pruritic scalp and affects up to half the world's population post-puberty. The aetiology of dandruff is multifactorial, influenced by Malassezia, sebum production and individual susceptibility. The commensal yeast Malassezia is a strong contributory factor to dandruff formation, but the presence of Malassezia on healthy scalps indicates that Malassezia alone is not a sufficient cause. A healthy stratum corneum (SC) forms a protective barrier to prevent water loss and maintain hydration of the scalp. It also protects against external insults such as microorganisms, including Malassezia, and toxic materials. Severe or chronic barrier damage can impair proper hydration, leading to atypical epidermal proliferation, keratinocyte differentiation and SC maturation, which may underlie some dandruff symptoms. The depleted and disorganized structural lipids of the dandruff SC are consistent with the weakened barrier indicated by elevated transepidermal water loss. Further evidence of a weakened barrier in dandruff includes subclinical inflammation and higher susceptibility to topical irritants. We are proposing that disruption of the SC of the scalp may facilitate dandruff generation, in part by affecting susceptibility to metabolites from Malassezia. Treatment of dandruff with cosmetic products to directly improve SC integrity while providing effective antifungal activity may thus be beneficial.

  5. LKB1 Regulates Cerebellar Development by Controlling Sonic Hedgehog-mediated Granule Cell Precursor Proliferation and Granule Cell Migration

    PubMed Central

    Men, Yuqin; Zhang, Aizhen; Li, Haixiang; Jin, Yecheng; Sun, Xiaoyang; Li, Huashun; Gao, Jiangang

    2015-01-01

    The Liver Kinase B1 (LKB1) gene plays crucial roles in cell differentiation, proliferation and the establishment of cell polarity. We created LKB1 conditional knockout mice (LKB1Atoh1 CKO) to investigate the function of LKB1 in cerebellar development. The LKB1Atoh1 CKO mice displayed motor dysfunction. In the LKB1Atoh1 CKO cerebellum, the overall structure had a larger volume and morelobules. LKB1 inactivationled to an increased proliferation of granule cell precursors (GCPs), aberrant granule cell migration and overproduction of unipolar brush cells. To investigate the mechanism underlying the abnormal foliation, we examined sonic hedgehog signalling (Shh) by testing its transcriptional mediators, the Gli proteins, which regulate the GCPs proliferation and cerebellar foliation during cerebellar development. The expression levels of Gli genes were significantly increased in the mutant cerebellum. In vitro assays showed that the proliferation of cultured GCPs from mutant cerebellum significantly increased, whereas the proliferation of mutant GCPs significantly decreased in the presence of a Shh inhibitor GDC-0049. Thus, LKB1 deficiency in the LKB1Atoh1 CKO mice enhanced Shh signalling, leading to the excessive GCP proliferation and the formation of extra lobules. We proposed that LKB1 regulates cerebellar development by controlling GCPs proliferation through Shh signalling during cerebellar development. PMID:26549569

  6. Postprostatectomy Erectile Dysfunction: A Review

    PubMed Central

    Salonia, Andrea; Briganti, Alberto; Montorsi, Francesco

    2016-01-01

    In the current era of the early diagnosis of prostate cancer (PCa) and the development of minimally invasive surgical techniques, erectile dysfunction (ED) represents an important issue, with up to 68% of patients who undergo radical prostatectomy (RP) complaining of postoperative erectile function (EF) impairment. In this context, it is crucial to comprehensively consider all factors possibly associated with the prevention of post-RP ED throughout the entire clinical management of PCa patients. A careful assessment of both oncological and functional baseline characteristics should be carried out for each patient preoperatively. Baseline EF, together with age and the overall burden of comorbidities, has been strongly associated with the chance of post-RP EF recovery. With this goal in mind, internationally validated psychometric instruments are preferable for ensuring proper baseline EF evaluations, and questionnaires should be administered at the proper time before surgery. Careful preoperative counselling is also required, both to respect the patient's wishes and to avoid false expectations regarding eventual recovery of baseline EF. The advent of robotic surgery has led to improvements in the knowledge of prostate surgical anatomy, as reflected by the formal redefinition of nerve-sparing techniques. Overall, comparative studies have shown significantly better EF outcomes for robotic RP than for open techniques, although data from prospective trials have not always been consistent. Preclinical data and several prospective randomized trials have demonstrated the value of treating patients with oral phosphodiesterase 5 inhibitors (PDE5is) after surgery, with the concomitant potential benefit of early re-oxygenation of the erectile tissue, which appears to be crucial for avoiding the eventual penile structural changes that are associated with postoperative neuropraxia and ultimately result in severe ED. For patients who do not properly respond to PDE5is, proper

  7. Postprostatectomy Erectile Dysfunction: A Review.

    PubMed

    Capogrosso, Paolo; Salonia, Andrea; Briganti, Alberto; Montorsi, Francesco

    2016-08-01

    In the current era of the early diagnosis of prostate cancer (PCa) and the development of minimally invasive surgical techniques, erectile dysfunction (ED) represents an important issue, with up to 68% of patients who undergo radical prostatectomy (RP) complaining of postoperative erectile function (EF) impairment. In this context, it is crucial to comprehensively consider all factors possibly associated with the prevention of post-RP ED throughout the entire clinical management of PCa patients. A careful assessment of both oncological and functional baseline characteristics should be carried out for each patient preoperatively. Baseline EF, together with age and the overall burden of comorbidities, has been strongly associated with the chance of post-RP EF recovery. With this goal in mind, internationally validated psychometric instruments are preferable for ensuring proper baseline EF evaluations, and questionnaires should be administered at the proper time before surgery. Careful preoperative counselling is also required, both to respect the patient's wishes and to avoid false expectations regarding eventual recovery of baseline EF. The advent of robotic surgery has led to improvements in the knowledge of prostate surgical anatomy, as reflected by the formal redefinition of nerve-sparing techniques. Overall, comparative studies have shown significantly better EF outcomes for robotic RP than for open techniques, although data from prospective trials have not always been consistent. Preclinical data and several prospective randomized trials have demonstrated the value of treating patients with oral phosphodiesterase 5 inhibitors (PDE5is) after surgery, with the concomitant potential benefit of early re-oxygenation of the erectile tissue, which appears to be crucial for avoiding the eventual penile structural changes that are associated with postoperative neuropraxia and ultimately result in severe ED. For patients who do not properly respond to PDE5is, proper

  8. HASHIMOTO THYROIDITIS AND VESTIBULAR DYSFUNCTION.

    PubMed

    Chiarella, Giuseppe; Russo, Diego; Monzani, Fabio; Petrolo, Claudio; Fattori, Bruno; Pasqualetti, Giuseppe; Cassandro, Ettore; Costante, Giuseppe

    2017-07-01

    The aim of this review was to analyze the existing literature concerning the relationship between Hashimoto thyroiditis (HT) and vestibular dysfunction. We used electronic databases (PubMed, EMBASE, Cochrane Library) to search and collect all published articles about the association between HT and vestibular disorders. Several observational and retrospective studies have postulated a relationship between thyroid autoimmunity and vestibular disorders. In most cases, an appropriate control group was lacking, and the impact of thyroid functional status could not precisely be established. In recent years, two well-designed prospective studies have provided convincing evidence that the association is not random. One article reported that patients with Ménière disease (MD) had a significantly higher prevalence of positive anti-thyroid autoantibody as compared to healthy controls. Moreover, more than half of MD patients had either positive anti-thyroid or non-organ-specific autoantibody titers, compared to less than 30% of both patients with unilateral vestibular paresis without cochlear involvement and healthy controls. Another study found that patients with benign paroxysmal positional vertigo (BPPV) had significantly higher serum thyroid-stimulating hormone and antithyroid autoantibody levels than healthy controls. Additionally, almost one-fifth of euthyroid patients with HT had signs of BPPV. The published results indicate that patients with MD or BPPV are potential candidates to also develop HT. Thus, in HT patients, the presence of even slight symptoms or signs potentially related to vestibular lesions should be carefully investigated. AITD = autoimmune thyroid disease; BPPV = benign paroxysmal positional vertigo; EH = endolymphatic hydrops; HT = Hashimoto thyroiditis; L-T4 = L-thyroxine; MD = Ménière disease; PS = Pendred syndrome; Tg = thyroglobulin; TPO = thyroid peroxidase; TSH = thyroid-stimulating hormone.

  9. Mitochondrial dysfunction in myofibrillar myopathy.

    PubMed

    Vincent, Amy E; Grady, John P; Rocha, Mariana C; Alston, Charlotte L; Rygiel, Karolina A; Barresi, Rita; Taylor, Robert W; Turnbull, Doug M

    2016-10-01

    Myofibrillar myopathies (MFM) are characterised by focal myofibrillar destruction and accumulation of myofibrillar elements as protein aggregates. They are caused by mutations in the DES, MYOT, CRYAB, FLNC, BAG3, DNAJB6 and ZASP genes as well as other as yet unidentified genes. Previous studies have reported changes in mitochondrial morphology and cellular positioning, as well as clonally-expanded, large-scale mitochondrial DNA (mtDNA) deletions and focal respiratory chain deficiency in muscle of MFM patients. Here we examine skeletal muscle from patients with desmin (n = 6), ZASP (n = 1) and myotilin (n = 2) mutations and MFM protein aggregates, to understand how mitochondrial dysfunction may contribute to the underlying mechanisms causing disease pathology. We have used a validated quantitative immunofluorescent assay to study respiratory chain protein levels, together with oxidative enzyme histochemistry and single cell mitochondrial DNA analysis, to examine mitochondrial changes. Results demonstrate a small number of clonally-expanded mitochondrial DNA deletions, which we conclude are due to both ageing and disease pathology. Further to this we report higher levels of respiratory chain complex I and IV deficiency compared to age matched controls, although overall levels of respiratory deficient muscle fibres in patient biopsies are low. More strikingly, a significantly higher percentage of myofibrillar myopathy patient muscle fibres have a low mitochondrial mass compared to controls. We concluded this is mechanistically unrelated to desmin and myotilin protein aggregates; however, correlation between mitochondrial mass and muscle fibre area is found. We suggest this may be due to reduced mitochondrial biogenesis in combination with muscle fibre hypertrophy.

  10. Cognitive dysfunction in mitochondrial disorders.

    PubMed

    Finsterer, J

    2012-07-01

    Among the various central nervous system (CNS) manifestations of mitochondrial disorders (MIDs), cognitive impairment is increasingly recognized and diagnosed (mitochondrial cognitive dysfunction). Aim of the review was to summarize recent findings concerning the aetiology, pathogenesis, diagnosis and treatment of cognitive decline in MIDs. Among syndromic MIDs due to mitochondrial DNA (mtDNA) mutations, cognitive impairment occurs in patients with mitochondrial encephalopathy, lactic acidosis and stroke-like episodes syndrome, myoclonus epilepsy with ragged-red fibres syndrome, mitochondrial chronic progressive external ophthalmoplegia, Kearns-Sayre syndrome, neuropathy, ataxia and retinitis pigmentosa syndrome and maternally inherited diabetes and deafness. Among syndromic MIDs due to nuclear DNA (nDNA) mutations, cognitive decline has been reported in myo-neuro-gastro-intestinal encephalopathy, mitochondrial recessive ataxia syndrome, spinocerebellar ataxia with encephalopathy, Mohr-Tranebjaerg syndrome, leuko-encephalopathy; brain and spinal cord involvement and lactic acidosis, CMT2, Wolfram syndrome, Wolf-Hirschhorn syndrome and Leigh syndrome. In addition to syndromic MIDs, a large number of non-syndromic MIDs due to mtDNA as well as nDNA mutations have been reported, which present with cognitive impairment as the sole or one among several other CNS manifestations of a MID. Delineation of mitochondrial cognitive impairment from other types of cognitive impairment is essential to guide the optimal management of these patients. Treatment of mitochondrial cognitive impairment is largely limited to symptomatic and supportive measures. Cognitive impairment may be a CNS manifestation of syndromic as well as non-syndromic MIDs. Correct diagnosis of mitochondrial cognitive impairment is a prerequisite for the optimal management of these patients. © 2012 John Wiley & Sons A/S.

  11. Long noncoding RNA-MEG3 is involved in diabetes mellitus-related microvascular dysfunction

    SciTech Connect

    Qiu, Gui-Zhen; Tian, Wei; Fu, Hai-Tao; Li, Chao-Peng; Liu, Ban

    2016-02-26

    Microvascular dysfunction is an important characteristic of diabetic retinopathy. Long non-coding RNAs (lncRNAs) play important roles in diverse biological processes. In this study, we investigated the role of lncRNA-MEG3 in diabetes-related microvascular dysfunction. We show that MEG3 expression level is significantly down-regulated in the retinas of STZ-induced diabetic mice, and endothelial cells upon high glucose and oxidative stress. MEG3 knockdown aggravates retinal vessel dysfunction in vivo, as shown by serious capillary degeneration, and increased microvascular leakage and inflammation. MEG3 knockdown also regulates retinal endothelial cell proliferation, migration, and tube formation in vitro. The role of MEG3 in endothelial cell function is mainly mediated by the activation of PI3k/Akt signaling. MEG3 up-regulation may serve as a therapeutic strategy for treating diabetes-related microvascular complications. - Highlights: • LncRNA-MEG3 level is down-regulated upon diabetic stress. • MEG3 knockdown aggravates retinal vascular dysfunction in vivo. • MEG3 regulates retinal endothelial cell function in vitro. • MEG3 regulates endothelial cell function through PI3k/Akt signaling.

  12. Erectile Dysfunction: A Sign of Heart Disease?

    MedlinePlus

    ... for heart disease before starting any treatment. Besides sharing a common disease process, erectile dysfunction and heart disease also share many risk factors, including: Diabetes. Men who have diabetes are ...

  13. Erectile dysfunction in the cardiovascular patient.

    PubMed

    Vlachopoulos, Charalambos; Jackson, Graham; Stefanadis, Christodoulos; Montorsi, Piero

    2013-07-01

    Erectile dysfunction is common in the patient with cardiovascular disease. It is an important component of the quality of life and it also confers an independent risk for future cardiovascular events. The usual 3-year time period between the onset of erectile dysfunction symptoms and a cardiovascular event offers an opportunity for risk mitigation. Thus, sexual function should be incorporated into cardiovascular disease risk assessment for all men. A comprehensive approach to cardiovascular risk reduction (comprising of both lifestyle changes and pharmacological treatment) improves overall vascular health, including sexual function. Proper sexual counselling improves the quality of life and increases adherence to medication. This review explores the critical connection between erectile dysfunction and cardiovascular disease and evaluates how this relationship may influence clinical practice. Algorithms for the management of patient with erectile dysfunction according to the risk for sexual activity and future cardiovascular events are proposed.

  14. Marital sexual dysfunction:introductory concepts.

    PubMed

    Levine, S B

    1976-04-01

    The concepts presented in this overview of marital sexual dysfunction are derived from increasing clinical experience with couples who seek help for their sexual problems. These couples, in marked contrast to couples with good sexual functioning, usually report a steady state of emotional dissatisfaction and minimal physical pleasure from sex. The affectual and behavioral consequences of persistent dysfunction are reviewed. Sexual therapy is discussed in terms of its two elements, sensate focus and psychotherapy. The various tastks which the sexual therapist may have to accomplish with individual couples are described. Consideration is given to the specific hypothese usually offered as explanation for sexual dysfunction-i.e., organic factors, varying degrees of relationship failure, poor communication, sexual ignorance, performance anxiety, and intrapsychic residua of past experience. A protocol for the screening physician to use in the formulation of a reasonable clinical plan for dysfunctional couples is included.

  15. Academic Achievement and Minimal Brain Dysfunction

    ERIC Educational Resources Information Center

    Edwards, R. Philip; And Others

    1971-01-01

    The investigation provided no evidence that a diagnosis of minimal brain dysfunction based on a pediatric neurological evaluation and/or visual-motor impairment as measured by the Bender-Gestalt, is a useful predictor of academic achievement. (Author)

  16. Hepatic Dysfunction in Typhoid Fever During Pregnancy

    PubMed Central

    Hasbun H., Jorge; Osorio, Raúl; Hasbun, Andrea

    2006-01-01

    We described the hepatic dysfunction found in 10 cases out of 32 women with typhoid fever during pregnancy. This was associated with late diagnosis and maternal and perinatal complications. PMID:17485807

  17. Osteoblast dysfunctions in bone diseases: from cellular and molecular mechanisms to therapeutic strategies.

    PubMed

    Marie, Pierre J

    2015-04-01

    Several metabolic, genetic and oncogenic bone diseases are characterized by defective or excessive bone formation. These abnormalities are caused by dysfunctions in the commitment, differentiation or survival of cells of the osteoblast lineage. During the recent years, significant advances have been made in our understanding of the cellular and molecular mechanisms underlying the osteoblast dysfunctions in osteoporosis, skeletal dysplasias and primary bone tumors. This led to suggest novel therapeutic approaches to correct these abnormalities such as the modulation of WNT signaling, the pharmacological modulation of proteasome-mediated protein degradation, the induction of osteoprogenitor cell differentiation, the repression of cancer cell proliferation and the manipulation of epigenetic mechanisms. This article reviews our current understanding of the major cellular and molecular mechanisms inducing osteoblastic cell abnormalities in age-related bone loss, genetic skeletal dysplasias and primary bone tumors, and discusses emerging therapeutic strategies to counteract the osteoblast abnormalities in these disorders of bone formation.

  18. Salivary gland dysfunction following radioactive iodine therapy

    SciTech Connect

    Wiesenfeld, D.; Webster, G.; Cameron, F.; Ferguson, M.M.; MacFadyen, E.E.; MacFarlane, T.W.

    1983-02-01

    Radioactive iodine is used extensively for the treatment of thyrotoxicosis and thyroid carcinoma. Iodine is actively taken up by the salivary glands and, following its use, salivary dysfunction may result as a consequence of radiation damage. The literature is reviewed and a case is reported in which a patient presented with a significant increase in caries rate attributed to salivary dysfunction following radioactive iodine therapy for a thyroid carcinoma.

  19. Towards an analysis of dysfunctional grammar.

    PubMed

    Rigaudeau-McKenna, B

    2005-01-01

    This article applies Systemic Functional Linguistics (SFL) to the study of language dysfunction. It demonstrates the potential that Systemic Functional analysis can offer to one aspect of the analysis of language dysfunction--the failure to realise complexes of clauses. For the purpose of analysis, new concepts and new measures have been created. The newly defined concepts and measures are illustrated in the discourse data of normally developing children and adolescents with brain injury.

  20. Erectile dysfunction: physiology, causes and patient management.

    PubMed

    Steggall, Martin J

    This article examines the prevalence, causes, identification, assessment and treatment options for men with erectile dysfunction. Erectile dysfunction is thought to affect one in ten men across the UK and is often a consequence of pathology and/or pharmacology. Treatment can be offered to all patients, but the keys to management are identification, accurate assessment and focused therapy. Nurses are well placed to identify and support men who have this distressing problem.

  1. [Endothelial dysfunction in pathogenesis of duodenal ulcer].

    PubMed

    Oparin, A G; Oparin, A A

    2002-01-01

    It is shown that in patients with ulcer associated with Helicobacter pylori (HP) there is a close correlation between the severity of the lesion of gastroduodenal protective mucous barrier and that of endothelial dysfunction manifesting in elevated level of endothelin-1, serum levels of TBK-active products, inhibition of blood flow and narrowing of the celiac trunk. The correlation becomes stronger with expanding contamination of gastroduodenal mucosa with HP. Thus, HP may participate in breaking the protective mucous barrier in endothelial dysfunction.

  2. The role of dysfunctional HDL in atherosclerosis

    PubMed Central

    Navab, Mohamad; Reddy, Srinivasa T.; Van Lenten, Brian J.; Anantharamaiah, G. M.; Fogelman, Alan M.

    2009-01-01

    This review focuses on HDL function in modulating LDL oxidation and LDL-induced inflammation. Dysfunctional HDL has been identified in animal models and humans with chronic inflammatory diseases including atherosclerosis. The loss of antiinflammatory function correlated with a loss of function in reverse cholesterol transport. In animal models and perhaps in humans, dysfunctional HDL can be improved by apoA-I mimetic peptides that bind oxidized lipids with high affinity. PMID:18955731

  3. [Bacterial flora in blepharitis].

    PubMed

    Bezza Benkaouha, I; Le Brun, C; Pisella, P-J; Chandenier, J; Lanotte, P

    2015-10-01

    Blepharitis has multiple, poorly defined origins. The goal of this study was to investigate the bacterial flora present in patients affected with blepharitis in comparison with healthy subjects, so as to understand the role of bacterial etiologies in blepharitis. Fifty-four patients with blepharitis and 50 healthy controls participated in this study. Swabs were obtained and analyzed qualitatively and quantitatively for bacteria. A subgroup of 16 people (9 with blepharitis and 7 controls) also were investigated for Demodex. The percentages of the positive cultures and the number of colonies/case were clearly higher for patients with blepharitis in comparison with healthy controls. Bacteria were isolated for 81% of cases versus 38% for controls, with a mean of 39 colonies versus 4.4 colonies for controls. Corynebacterium sp. were the most common microorganisms isolated from patients with blepharitis (53.7% for cases versus 18% for controls, P<0.01), and the bacterial load was 15 times higher (37.4 col/case versus 2.6 col/case). C. macginleyi was the most common Corynebacteria (33% versus 6%, P<0.01). S. epidermidis: 35.1% versus 16% (P=0.02) with 11.3 col/case versus 1.6 col/case. S. aureus: 13% versus 0% (P=0.01) with 24.7 col/case versus 0. We did not find a significant difference for Propionibacterium acnes: 14.8% versus 14% with 4.7 col/case versus 5.1 col/case, or for Demodex, with 22.2% versus 28.6%. Corynebacterium sp. and especially C. macginleyi seem to participate actively in the physiopathology of blepharitis. S. epidermidis and S. aureus also remain associated with this pathology. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  4. [The bacterial nucleoid].

    PubMed

    Gómez-Eichelmann, M C; Camacho-Carranza, R

    1995-01-01

    The bacterial genome is present in the cell within a complex structure, the nucleoid. The nucleoid contains the genomic DNA, and molecules of RNA and proteins. The main proteins of the nucleoid are: RNA polymerase, topoisomerases and the histone-like proteins: HU, H-NS (H1), H, HLP1, IHF and FIS. The DNA molecule in the nucleoid is under helical tension or supercoiling and is organized into 43 +/- 10 topodomains. DNA supercoiling is generated by the activity of the topoisomerases and by DNA-protein interactions. In this review, we analize current knowledge in Escherichia coli about genome organization and proteins of the nucleoid.

  5. Bundling of bacterial flagella

    NASA Astrophysics Data System (ADS)

    Powers, Thomas R.; van Parys, Annemarie J.; Breuer, Kenneth S.

    2002-03-01

    In bacterial chemotaxis, cells such as E. coli drift up chemical gradients by means of a directed random walk. Near the beginning of each step of a walk, the rotating helical flagella which propel the cell form a bundle. Using macroscopic experiments and numerical calculations, we study the viscous flows set up by two rotating helices. Our work illustrates the importance of geometry; for example, left-handed helices rotating counter-clockwise when viewed from the distal ends will inter-penetrate and synchronize when the pitch is shorter than the circumference. When the same helices turn clockwise, they fail to inter-penetrate.

  6. [Lower urinary tract dysfunction following radical hysterectomy].

    PubMed

    Aoun, F; Roumeguère, T

    2015-12-01

    Radical hysterectomy is associated with a significant amount of urinary functional complications and a negative impact on quality of life. The aim of this review is to provide a comprehensive overview of the neurological etiology of lower urinary tract dysfunction following radical hysterectomy and to establish an optimal postoperative management strategy. We performed a comprehensive overview using the following terms: "radical hysterectomy" and "urologic diseases etiology" or "urologic disease prevention and control". The reported incidence of lower urinary tract dysfunction after radical hysterectomy varies from 12 to 85%. Several animal and clinical urodynamic studies corroborate the neurologic etiology of the dysfunction. Lower urinary tract dysfunction is a common postoperative finding (70-85%) but spontaneous recovery is to be expected within 6-12 months after surgery. The most frequent long term sequela is stress urinary incontinence (40% of cases) and its management is complex and challenging. Postoperative refractory overactive bladder and bladder underactivity can be treated by neuromodulation of sacral roots and superior hypogastric plexus, respectively. In the absence of good clinical predictors, preoperative urodynamic examinations could have a role in understanding the pathophysiology of the dysfunction before such interventions. The pathophysiology of lower urinary tract dysfunction following radical hysterectomy is multifactorial. Its management is complex and should be multidisciplinary. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  7. Thyroid hormone dysfunction during pregnancy: A review

    PubMed Central

    Alemu, Aynadis; Terefe, Betelihem; Abebe, Molla; Biadgo, Belete

    2016-01-01

    Thyroid dysfunctions such as hypothyroidism, thyrotoxicosis and thyroid nodules may develop during pregnancy leading to abortion, placental abruptions, preeclampsia, preterm delivery and reduced intellectual function in the offspring. Epidemiological data have shown the significant role of maternal thyroid hormone in fetal neurologic development and maternal health. It has been suggested that the deleterious effects of thyroid dysfunction can also extend beyond pregnancy and delivery to affect neuro-intellectual development in the early life of the child. Pregnancy poses an important challenge to the maternal thyroid gland as hormone requirements are increased during gestation as a result of an increase in thyroid- binding globulin, the stimulatory effect of HCG on TSH receptors, and increased peripheral thyroid hormone requirements. Maternal thyroid dysfunction is associated with increased risk for early abortion, preterm delivery, neonatal morbidity and other obstetrical complications. Early diagnosis for thyroid dysfunction of pregnant women and treatment of thyroid dysfunction during pregnancy is important and cost effective to avoid both fetal and maternal complications secondary to thyroid dysfunction. Therefore the aim of this review was to assess the thyroid function changes occurring during pregnancy, the different disorders with their maternal and fetal implications, the laboratory diagnosis and the best ways of management of these conditions. PMID:27981252

  8. Major depressive disorder, antidepressants, and sexual dysfunction.

    PubMed

    Clayton, Anita H; Montejo, Angel L

    2006-01-01

    Sexual dysfunction is a common problem with a number of causes, including psychosocial factors, general medical illness, psychiatric disorders, and psychotropic and nonpsychiatric medications. It is especially prevalent among patients with poor emotional health and has been strongly associated with antidepressant medications. Selective serotonin reuptake inhibitors (SSRIs) in particular have demonstrated a higher incidence of sexual dysfunction than other antidepressants that work through different mechanisms of action. Further supporting the relationship between sexual dysfunction and antidepressant mechanism of action, data from a number of studies indicate that bupropion, nefazodone, and mirtazapine alleviate symptoms of sexual dysfunction and are as effective as SSRIs at controlling depressive symptoms. Although a number of strategies besides drug substitution have been utilized to help manage antidepressant-induced sexual dysfunction, many patients remain suboptimally treated; as many as 42% of patients were found to passively wait for spontaneous remission. The addition of antidotal therapy has been proven to be among the effective management strategies for sexual dysfunction. However, due to a lack of systematic data, additional studies are warranted to further investigate these findings.

  9. Vascular endothelial dysfunction and pharmacological treatment

    PubMed Central

    Su, Jin Bo

    2015-01-01

    The endothelium exerts multiple actions involving regulation of vascular permeability and tone, coagulation and fibrinolysis, inflammatory and immunological reactions and cell growth. Alterations of one or more such actions may cause vascular endothelial dysfunction. Different risk factors such as hypercholesterolemia, homocystinemia, hyperglycemia, hypertension, smoking, inflammation, and aging contribute to the development of endothelial dysfunction. Mechanisms underlying endothelial dysfunction are multiple, including impaired endothelium-derived vasodilators, enhanced endothelium-derived vasoconstrictors, over production of reactive oxygen species and reactive nitrogen species, activation of inflammatory and immune reactions, and imbalance of coagulation and fibrinolysis. Endothelial dysfunction occurs in many cardiovascular diseases, which involves different mechanisms, depending on specific risk factors affecting the disease. Among these mechanisms, a reduction in nitric oxide (NO) bioavailability plays a central role in the development of endothelial dysfunction because NO exerts diverse physiological actions, including vasodilation, anti-inflammation, antiplatelet, antiproliferation and antimigration. Experimental and clinical studies have demonstrated that a variety of currently used or investigational drugs, such as angiotensin-converting enzyme inhibitors, angiotensin AT1 receptors blockers, angiotensin-(1-7), antioxidants, beta-blockers, calcium channel blockers, endothelial NO synthase enhancers, phosphodiesterase 5 inhibitors, sphingosine-1-phosphate and statins, exert endothelial protective effects. Due to the difference in mechanisms of action, these drugs need to be used according to specific mechanisms underlying endothelial dysfunction of the disease. PMID:26635921

  10. Identification of transcriptional networks involved in peroxisome proliferator chemical-induced hepatocyte proliferation

    EPA Science Inventory

    Peroxisome proliferator chemical (PPC) exposure leads to increases in rodent liver tumors through a non-genotoxic mode of action (MOA). The PPC MOA includes increased oxidative stress, hepatocyte proliferation and decreased apoptosis. We investigated the putative genetic regulato...

  11. Identification of transcriptional networks involved in peroxisome proliferator chemical-induced hepatocyte proliferation

    EPA Science Inventory

    Peroxisome proliferator chemical (PPC) exposure leads to increases in rodent liver tumors through a non-genotoxic mode of action (MOA). The PPC MOA includes increased oxidative stress, hepatocyte proliferation and decreased apoptosis. We investigated the putative genetic regulato...

  12. Propionibacterium acnes lacks the capability to proliferate in platelet concentrates.

    PubMed

    Störmer, M; Kleesiek, K; Dreier, J

    2008-04-01

    Propionibacterium acnes is considered to be one of the most frequent contaminants of platelet concentrates (PCs) when anaerobic culture-based detection methods are used. But Propionibacteria are often detected too late when blood products have already been transfused. Therefore, its transfusion relevance is still demanding clarification because studies of the outcome of patients transfused with P. acnes-contaminated PCs are still uncommon. In this study, we monitored clinical effects in patients after transfusion of PCs, which were detected too late in sterility testing. Furthermore, we assessed the bacterial proliferation of Propionibacterium species seeded into PCs to clarify their significance for platelet bacteria screening. In the look-back process, we followed the route of the putative contaminated PC units from storage to transfusion. In the in vitro study, PCs were inoculated with 1-100 colony-forming unit (CFU)/ml of clinical isolates of Propionibacteria (n = 10). Sampling was performed during 10-day aerobic storage at 22 degrees C. The presence of bacteria was assessed by plating culture and automated BacT/Alert culture system. Propionibacterium acnes shows slow or no growth under PC storage conditions. Clinical signs of adverse events after transfusion of potentially contaminated PC units were not reported. Propionibacteria do not proliferate under PC storage conditions and therefore may be missed or detected too late when blood products have already been transfused.

  13. Berberine attenuates cardiac dysfunction in hyperglycemic and hypercholesterolemic rats.

    PubMed

    Dong, Shi-Fen; Hong, Ying; Liu, Ming; Hao, Ying-Zhi; Yu, Hai-Shi; Liu, Yang; Sun, Jian-Ning

    2011-06-25

    The positive effects of berberine (30 mg/kg/day, i.g. for 6 weeks) on cardiac dysfunction were evaluated in the rat model of hyperglycemia and hypercholesterolemia. Hyperglycemia and hypercholesterolemia were induced by feeding high-sucrose/fat diet (HSFD) consisting of 20% sucrose, 10% lard, 2.5% cholesterol, 1% bile salt for 12 weeks and streptozotocin (30 mg/kg, i.p.). The plasma sugar, total cholesterol, and triglyceride levels were significantly increased (422, 194 and 82%, respectively) in the HSFD/streptozotocin-treated rats, when compared with control animals receiving normal diet and vehicle. Berberine treatment reduced the plasma sugar and lipid levels by 24-69% in the rat model of hyperglycemia and hypercholesterolemia. Cardiac functions signed as values of cardiac output, left ventricular systolic pressure, the maximum rate of myocardial contraction (+dp/dtmax), left ventricular end diastolic pressure and the maximum rate of myocardial diastole (-dp/dtmax) were injured by 16-55% in the hyperglycemic/hypercholesterolemic rats. Berberine increased cardiac output, left ventricular systolic pressure and +dp/dtmax by 64, 16 and 79%, but decreased left ventricular end diastolic pressure and -dp/dtmax by 121 and 61% in the rats receiving HSFD/streptozotocin, respectively, when compared with the drug-untreated rats of hyperglycemia and hypercholesterolemia. Berberine caused significant increase in cardiac fatty acid transport protein-1 (159%), fatty acid transport proteins (56%), fatty acid beta-oxidase (52%), as well as glucose transporter-4 and peroxisome proliferator-activated receptor-γ (PPARγ), but decrease in PPARα mRNA and protein expression in hyperglycemic/hypercholesterolemic rats. These results indicated that berberine exerted protective effects on cardiac dysfunction induced by hyperglycemia/hypercholesterolemia through alleviating cardiac lipid accumulation and promoting glucose transport.

  14. Arterial ageing: from endothelial dysfunction to vascular calcification.

    PubMed

    Tesauro, M; Mauriello, A; Rovella, V; Annicchiarico-Petruzzelli, M; Cardillo, C; Melino, G; Di Daniele, N

    2017-05-01

    Complex structural and functional changes occur in the arterial system with advancing age. The aged artery is characterized by changes in microRNA expression patterns, autophagy, smooth muscle cell migration and proliferation, and arterial calcification with progressively increased mechanical vessel rigidity and stiffness. With age the vascular smooth muscle cells modify their phenotype from contractile to 'synthetic' determining the development of intimal thickening as early as the second decade of life as an adaptive response to forces acting on the arterial wall. The increased permeability observed in intimal thickening could represent the substrate on which low-level atherosclerotic stimuli can promote the development of advanced atherosclerotic lesions. In elderly patients the atherosclerotic plaques tend to be larger with increased vascular stenosis. In these plaques there is a progressive accumulation of both lipids and collagen and a decrease of inflammation. Similarly the plaques from elderly patients show more calcification as compared with those from younger patients. The coronary artery calcium score is a well-established marker of adverse cardiovascular outcomes. The presence of diffuse calcification in a severely stenotic segment probably induces changes in mechanical properties and shear stress of the arterial wall favouring the rupture of a vulnerable lesion in a less stenotic adjacent segment. Oxidative stress and inflammation appear to be the two primary pathological mechanisms of ageing-related endothelial dysfunction even in the absence of clinical disease. Arterial ageing is no longer considered an inexorable process. Only a better understanding of the link between ageing and vascular dysfunction can lead to significant advances in both preventative and therapeutic treatments with the aim that in the future vascular ageing may be halted or even reversed. © 2017 The Association for the Publication of the Journal of Internal Medicine.

  15. Bacterial biosorbents and biosorption.

    PubMed

    Vijayaraghavan, K; Yun, Yeoung-Sang

    2008-01-01

    Biosorption is a technique that can be used for the removal of pollutants from waters, especially those that are not easily biodegradable such as metals and dyes. A variety of biomaterials are known to bind these pollutants, including bacteria, fungi, algae, and industrial and agricultural wastes. In this review, the biosorption abilities of bacterial biomass towards dyes and metal ions are emphasized. The properties of the cell wall constituents, such as peptidoglycan, and the role of functional groups, such as carboxyl, amine and phosphonate, are discussed on the basis of their biosorption potentials. The binding mechanisms, as well as the parameters influencing the passive uptake of pollutants, are analyzed. A detailed description of isotherm and kinetic models and the importance of mechanistic modeling are presented. A systematic comparison of literature, based on the metal/dye binding capacity of bacterial biomass under different conditions, is also provided. To enhance biosorption capacity, biomass modifications through chemical methods and genetic engineering are discussed. The problems associated with microbial biosorption are analyzed, and suitable remedies discussed. For the continuous treatment of effluents, an up-flow packed column configuration is suggested and the factors influencing its performance are discussed. The present review also highlights the necessity for the examination of biosorbents within real situations, as competition between solutes and water quality may affect the biosorption performance. Thus, this article reviews the achievements and current status of biosorption technology, and hopes to provide insights into this research frontier.

  16. Bacterial proteases and virulence.

    PubMed

    Frees, Dorte; Brøndsted, Lone; Ingmer, Hanne

    2013-01-01

    Bacterial pathogens rely on proteolysis for variety of purposes during the infection process. In the cytosol, the main proteolytic players are the conserved Clp and Lon proteases that directly contribute to virulence through the timely degradation of virulence regulators and indirectly by providing tolerance to adverse conditions such as those experienced in the host. In the membrane, HtrA performs similar functions whereas the extracellular proteases, in close contact with host components, pave the way for spreading infections by degrading host matrix components or interfering with host cell signalling to short-circuit host cell processes. Common to both intra- and extracellular proteases is the tight control of their proteolytic activities. In general, substrate recognition by the intracellular proteases is highly selective which is, in part, attributed to the chaperone activity associated with the proteases either encoded within the same polypeptide or on separate subunits. In contrast, substrate recognition by extracellular proteases is less selective and therefore these enzymes are generally expressed as zymogens to prevent premature proteolytic activity that would be detrimental to the cell. These extracellular proteases are activated in complex cascades involving auto-processing and proteolytic maturation. Thus, proteolysis has been adopted by bacterial pathogens at multiple levels to ensure the success of the pathogen in contact with the human host.

  17. Bacterial trapping in shear

    NASA Astrophysics Data System (ADS)

    Rusconi, Roberto; Guasto, Jeffrey S.; Stocker, Roman

    2012-11-01

    Bacteria are ubiquitously exposed to flow, both in natural environments and artificial devices (e.g., catheters), where confining surfaces create non-uniform shear. While the effects of shear on passive particles are well understood, little is known about the consequences of shear on motile bacteria. We exposed bacteria having different motility strategies (e.g., run-and-tumble, run-and-reverse) to microfluidic Poiseuille flows and quantified the swimming kinematics and cell distribution in the channel using video-microscopy. We discovered that the coupling of motility and a spatially varying shear results in a dramatic trapping of motile cells in high-shear regions, and conversely a strong depletion in the low-shear portion of the channel. We demonstrate experimentally that this trapping process is robust across species such as Bacillus subtilis and Pseudomonas aeruginosa, and can have far-reaching consequences on bacterial transport, by (i) counteracting bacterial chemotactic responses; and (ii) enhancing surface attachment and thus biofilm formation by trapping cells near walls. More generally, this work shows that-despite the low Reynolds number-the coupling of flow and self-propulsion can be nonlinear and not simply a superposition of the two effects.

  18. Mechanism of Bacterial Oligosaccharyltransferase

    PubMed Central

    Gerber, Sabina; Lizak, Christian; Michaud, Gaëlle; Bucher, Monika; Darbre, Tamis; Aebi, Markus; Reymond, Jean-Louis; Locher, Kaspar P.

    2013-01-01

    N-Linked glycosylation is an essential post-translational protein modification in the eukaryotic cell. The initial transfer of an oligosaccharide from a lipid carrier onto asparagine residues within a consensus sequon is catalyzed by oligosaccharyltransferase (OST). The first X-ray structure of a complete bacterial OST enzyme, Campylobacter lari PglB, was recently determined. To understand the mechanism of PglB, we have quantified sequon binding and glycosylation turnover in vitro using purified enzyme and fluorescently labeled, synthetic peptide substrates. Using fluorescence anisotropy, we determined a dissociation constant of 1.0 μm and a strict requirement for divalent metal ions for consensus (DQNAT) sequon binding. Using in-gel fluorescence detection, we quantified exceedingly low glycosylation rates that remained undetected using in vivo assays. We found that an alanine in the −2 sequon position, converting the bacterial sequon to a eukaryotic one, resulted in strongly lowered sequon binding, with in vitro turnover reduced 50,000-fold. A threonine is preferred over serine in the +2 sequon position, reflected by a 4-fold higher affinity and a 1.2-fold higher glycosylation rate. The interaction of the +2 sequon position with PglB is modulated by isoleucine 572. Our study demonstrates an intricate interplay of peptide and metal binding as the first step of protein N-glycosylation. PMID:23382388

  19. The bacterial gliding machinery

    NASA Astrophysics Data System (ADS)

    Shrivastava, Abhishek

    Cells of Flavobacterium johnsoniae, a rod-shaped bacterium, glide over surfaces with speeds reaching up to 2 micrometer's. Gliding is powered by a protonmotive force. The adhesin SprB forms filaments about 160 nm long that move on the cell-surface along a looped track. Interaction of SprB filaments with a surface produces gliding. We tethered F. johnsoniae cells to glass by adding anti-SprB antibody. Tethered cells spun about fixed points, rotating at speeds of about 1 Hz. The torques required to sustain such speeds were large, comparable to those generated by the flagellar rotary motor. Using a flow cell apparatus, we changed load on the gliding motor by adding the viscous agent Ficoll to tethered cells. We found that a gliding motor runs at constant speed rather than constant torque. We attached gold nanoparticles to the SprB filament and tracked its motion. We fluorescently tagged a bacterial Type IX secretion system (T9SS) protein and imaged its dynamics. Fluorescently tagged T9SS protein localized near the point of tether, indicating that T9SS localizes with the gliding motor. Based on our results, we propose a model to explain bacterial gliding.

  20. Optimality in Bacterial Chemotaxis

    NASA Astrophysics Data System (ADS)

    Vladimirov, Nikita; Lebiedz, Dirk; Sourjik, Victor

    2010-03-01

    One of the central questions of systems biology is the role of microscopic parameters of a single cell in the behavior of population. Multiscale models address this problem, allowing us to understand population behavior from single-cell molecular components and reactions. In this work a multiscale (hybrid) model is presented, which describes chemotactic Escherichia coli bacterium by combination of mathematical models and time-scale separation of key reactions. The bacterial behavior is described with high accuracy according to the available experimental data. The model shows several new aspects of chemotactic optimality in terms of adaptation rate, gradient steepness and type of medium (liquid or porous). Also, it predicts existence of an additional mechanism of gradient navigation in E. coli. Based on the available experiments, the model suggests that tumbles are anisotropic, i.e. the angle of reorientation during a tumble depends on the swimming direction along the gradient. This result demonstrates a new level of optimization in E. coli chemotaxis, which is likely to be used by some other peritrichously flagellated bacteria, and indicates yet another level of evolutionary optimization in bacterial chemotaxis.